[go: up one dir, main page]

CN105367528A - A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl)oxy-1-acetone compound and its synthesis method - Google Patents

A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl)oxy-1-acetone compound and its synthesis method Download PDF

Info

Publication number
CN105367528A
CN105367528A CN201510758692.0A CN201510758692A CN105367528A CN 105367528 A CN105367528 A CN 105367528A CN 201510758692 A CN201510758692 A CN 201510758692A CN 105367528 A CN105367528 A CN 105367528A
Authority
CN
China
Prior art keywords
cycloalkane
tetrahydropyranyl
compound
secondary amino
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201510758692.0A
Other languages
Chinese (zh)
Inventor
赵东平
王贯峰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nantong Nuotai Biological Pharmaceutical Co ltd
Original Assignee
Nantong Nuotai Biological Pharmaceutical Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nantong Nuotai Biological Pharmaceutical Co ltd filed Critical Nantong Nuotai Biological Pharmaceutical Co ltd
Priority to CN201510758692.0A priority Critical patent/CN105367528A/en
Publication of CN105367528A publication Critical patent/CN105367528A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/10—Oxygen atoms
    • C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明公开了一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物，其结构通式为：其中，n=1~5。该化合物Ⅰ的制备方法，包括以下步骤：（1）N2保护下，D-乳酸甲酯与环烷仲胺在30~60°C下，以环烷仲胺作为溶剂反应，制得关键中间体Ⅱ；（2）N2保护下，中间体Ⅱ溶于有机溶剂中，与3,4-二氢吡喃以有机强酸作为催化剂，室温反应，制得化合物Ⅰ，其中n=1~5。这类化合物不仅结构新颖、而且合成步骤简单、产率高、生产成本低。The present invention discloses a triazole drug intermediate (D)-1-(1-cycloalkyl secondary amino)-2-(2-tetrahydropyranyl)oxy-1-acetone compound, the general structural formula of which is: Wherein, n=1~5. The preparation method of the compound I comprises the following steps: (1) under N2 protection, D-lactate methyl ester reacts with cycloalkane secondary amine at 30~60°C, using cycloalkane secondary amine as solvent, to obtain a key intermediate II; (2) under N2 protection, intermediate II is dissolved in an organic solvent, reacts with 3,4-dihydropyran using an organic strong acid as a catalyst, and reacts at room temperature to obtain compound I, wherein n=1~5. This type of compound not only has a novel structure, but also has simple synthesis steps, high yield, and low production cost.

Description

A kind of triazole type medicine intermediate (D)-1-(1-cycloalkanes secondary amine)-2-(2-THP trtrahydropyranyl) oxygen-1-acetone compounds and synthetic method
Technical field
The present invention relates to medical art, specifically a kind of triazole type medicine intermediate (D)-1-(1-cycloalkanes secondary amine)-2-(2-THP trtrahydropyranyl) oxygen-1-acetone compounds and synthetic method.
Background technology
Fungi infestation sickness rate continues to rise, and has become the one of the main reasons causing global infectious diseases associated death.Triazole type medicine is a large primary categories of current antifungal drug, common triazole type medicine comprises as Chinese mugwort Saperconazole (Isavuconazole), in fluconazole (Ravuconazole), Chinese mugwort fluconazole (Efinaconazole), albaconazole (Albaconazole) etc.Existing these medicines of synthesis method has route more complicated, reaction yield is low, solvent is expensive, have toxicity, security is low, be difficult to the shortcomings such as industrialization, as international monopoly PCTInt.Appl., 2005014583, PCTInt.Appl., 9839305, all adopt morpholine to react as reaction reagent and methyl lactate, reactions steps is loaded down with trivial details, need to add reaction solvent in addition, reaction yield is lower, and reaction process need add other organic solvents.
Summary of the invention
The invention provides a kind of triazole type medicine intermediate (D)-1-(1-cycloalkanes secondary amine)-2-(2-THP trtrahydropyranyl) oxygen-1-acetone compounds and synthetic method, such compou nd synthesis method is simple, and reaction conversion ratio is high.
The technical solution used in the present invention is: a kind of triazole type medicine intermediate (D)-1-(1-cycloalkanes secondary amine)-2-(2-THP trtrahydropyranyl) oxygen-1-acetone compounds, and it is characterized in that, this compound structure general formula is as follows: , wherein, n=1 ~ 5.
The preparation method of above-claimed cpd I, comprises the following steps: (1) N 2under protection, D-ALPHA-Hydroxypropionic acid methyl esters and cycloalkanes secondary amine under 30 ~ 60 ° of C, preferably 40 ~ 50 ° of C; using cycloalkanes secondary amine as solvent reaction, obtained key intermediate II, wherein; the mol ratio of D-ALPHA-Hydroxypropionic acid methyl esters and cycloalkanes secondary amine is 1:1 ~ 1:1.3, preferred 1:1 ~ 1:1.1, more preferably 1:1.05.
(2) N 2under protection, intermediate II is dissolved in organic solvent, with 3; 4-dihydropyrane is using organic acid as catalyzer, and room temperature reaction, obtains chemical compounds I; wherein n=1 ~ 5, the mol ratio of intermediate II and catalyzer is 1:0.05 ~ 0.1, preferred 1:0.08 ~ 0.1; more preferably 1:0.1; the mol ratio of intermediate II and 3,4-dihydropyrane is 1:1 ~ 1:1.4, preferred 1:1 ~ 1.3; more preferably 1:1.1, reaction formula is as follows:
。
Preferably, described cycloalkanes secondary amine is Pyrrolidine.
Preferably, in step (2), described organic acid is tosic acid or methylsulfonic acid, and described organic solvent is tetrahydrofuran (THF).
In step (2), during dropping catalyzer, temperature of reaction is no more than 0 ° of C, and during dropping 3,4-dihydropyrane, temperature of reaction is no more than 20 ° of C, and when the complete temperature of reaction of all reagent dropwise controls at 25 ° of C, the reaction times is 5 ~ 6h.
Advantage of the present invention: in the present invention, this compounds not only novel structure, synthesis step is simple, reaction conversion ratio is high, step (1) does not need another solubilizing agent in reaction process, reduce the cost of reaction, therefore great exploitation potential for its and good application prospect.
Embodiment
In order to deepen the understanding of the present invention, below in conjunction with embodiment, the invention will be further described, and this embodiment only for explaining the present invention, does not form limiting the scope of the present invention.
Embodiment 1:
(1) synthesis (n=2) of intermediate II: add 360Kg (3.46Kmol) D-ALPHA-Hydroxypropionic acid methyl esters in the reactor of 1000L, logical nitrogen protection, drips 246Kg Pyrrolidine (1.0eq), stirring reaction 8h under 45 ° of C.Concentrate the by-product carbinol that major part reaction produces, add 12.3Kg Pyrrolidine (0.05eq), nitrogen protection, under 40 ~ 50 ° of C, continue reaction 5h.Concentrated by reaction solution, obtain orange-yellow oily liquids (D)-1-(1-pyrrolidyl)-2-hydroxyl-1-acetone 490Kg (theoretical yield 495Kg), i.e. intermediate II, yield is 98.99%.Product is dissolved in deuterochloroform, is characterized by proton nmr spectra, and each peak ownership is as follows, 1.39 (d, 3 Η), 1.97 (q, 4H), 3.46 (q, 4H), 4.34 (q, 1H).Product structure formula is as follows:
。
(2) preparation (n=2) of chemical compounds I: 490Kg the first step product, joins in the reactor of 1000L, adds 700L tetrahydrofuran (THF), passes into nitrogen protection.Add tosic acid 59Kg (0.1eq), temperature is not more than 0 ° of C in batches.Then drip 3, the 4-dihydropyrane (1.1eq) of 318Kg, control temperature is no more than 20 ° of C, drips off rear 25 ° of C reaction.Monitoring reaction after 5h, after question response is complete, with the Na of 12% 2cO 3(400Kg) aqueous solution cancellation reaction, leave standstill 30min separatory, the tertiary fourth methyl ether back extraction of water layer 300L, merge organic layer, the salt solution 300Kg with 15% washs once, organic layer 25Kg anhydrous sodium sulfate drying 2h, filter, filtrate obtains 770Kg pale yellowish oil liquid (D)-1-(1-pyrrolidyl)-2-(2-THP trtrahydropyranyl) oxygen-1-acetone at 30 ~ 55 ° of C decompression precipitations, i.e. chemical compounds I, yield is 97.47%.Product is dissolved in deuterochloroform, is characterized by proton nmr spectra, and each peak ownership is as follows, 1.39 (d, 3H), 1.55 ~ 1.65 (m, 6H), 1.97 (q, 4H), 3.46 (q, 4H), 3.55 (t, 2H), 3.96 (q, 1H), 4.95 (t, 1H).Product structure formula is as follows:
。
Embodiment 2:
(1) synthesis (n=3) of intermediate II: add 360Kg (3.46Kmol) D-ALPHA-Hydroxypropionic acid methyl esters in the reactor of 1000L, logical nitrogen protection, drips 294.62Kg piperidines (1.0eq), stirring reaction 8h under 45 ° of C.Concentrate most of by-product carbinol in reaction solution, add 14.73Kg piperidines (0.05eq), nitrogen protection, under 45 ° of C, continue reaction 5h.Concentrated by reaction solution, obtain orange-yellow oily liquids (D)-1-(1-piperidines alkyl)-2-hydroxyl-1-acetone 535Kg (theoretical yield 543Kg), i.e. intermediate II, yield is 98.53%.Product is dissolved in deuterochloroform, is characterized by proton nmr spectra, and each peak ownership is as follows, 1.39 (d, 3H), 1.50-1.55 (m, 6H), 3.34 (t, 4H), 4.34 (q, 1H).Product structure formula is as follows:
。
(2) preparation (n=3) of chemical compounds I: 535Kg intermediate II joins in the reactor of 1000L; add 750L tetrahydrofuran (THF); pass into nitrogen protection; add tosic acid 58.7Kg (0.1eq) in batches; temperature, more than 0 ° of C, then drips 3, the 4-dihydropyrane (1.1eq) of 315.5Kg; control temperature is no more than 20 ° of C, drips off rear 25 ° of C reaction.Monitoring reaction after 5h, after question response is complete, with the Na of 12% 2cO 3(400Kg) aqueous solution cancellation reaction, leave standstill 30min separatory, the tertiary fourth methyl ether back extraction of water layer 300L, merge organic layer, the salt solution 300Kg with 15% washs once, organic layer 25Kg anhydrous sodium sulfate drying 2h, filter, filtrate obtains 785Kg pale yellowish oil (D)-1-(1-piperidines alkyl)-2-(2-THP trtrahydropyranyl) oxygen-1-acetone at 30 ~ 55 ° of C decompression precipitations, i.e. chemical compounds I, yield is 95.97%.Product is dissolved in deuterochloroform, is characterized by proton nmr spectra, and each peak ownership is as follows, 1.39 (d, 3H), 1.50-1.55 (m, 6H), 1.55 ~ 1.65 (m, 6H), 3.34 (q, 4H), 3.55 (t, 2H), 3.96 (q, 1H), 4.95 (t, 1H).Product structure formula is as follows:
。
Embodiment 3:
(1) synthesis (n=1) of intermediate II: add 360Kg (3.46Kmol) D-ALPHA-Hydroxypropionic acid methyl esters in the reactor of 1000L, logical nitrogen protection, drip 198Kg azetidine (1.0eq), stirring reaction 8h under 40 ° of C, concentrate most of by-product carbinol in reaction solution, add 9.88Kg azetidine (0.05eq), nitrogen protection, reaction 5h is continued under 40 ° of C, reaction solution is concentrated, obtain orange-yellow oily liquids (D)-1-(1-azo-cycle butane group)-2-hydroxyl-1-acetone 200Kg(theoretical yield 446Kg), yield is 44.84%, product is dissolved in deuterochloroform, characterized by proton nmr spectra, following 1.39 (the d of each peak ownership, 3H), 2.20-2.23 (m, 2H), 3.34 (t, 4H), 4.34 (q, 1H), product structure formula is as follows:
。
(2) preparation (n=1) of chemical compounds I: 200Kg the first step product (D)-1-(1-azo-cycle butane group)-2-hydroxyl-1-acetone is joined in the reactor of 500L, add 300L tetrahydrofuran (THF), pass into nitrogen protection, add tosic acid 26.66Kg (0.1eq) in batches, temperature is not more than 0 ° of C, then 3 of 143Kg are dripped, 4-dihydropyrane (1.1eq), control temperature is no more than 20 ° of C, drip off rear 25 ° of C reaction, monitoring reaction after 5h, after question response is complete, with the Na of 12% 2cO 3(200Kg) aqueous solution cancellation reaction, leave standstill 30min separatory, the tertiary fourth methyl ether back extraction of water layer 150L, merge organic layer, salt solution 100Kg with 15% washs once, organic layer 10Kg anhydrous sodium sulfate drying 2h, filter, filtrate obtains 200Kg pale yellowish oil (D)-1-(1-azetidinyl)-2-(2-THP trtrahydropyranyl) oxygen-1-acetone at 30 ~ 55 ° of C decompression precipitations, yield is 60.61%, product is dissolved in deuterochloroform, characterized by proton nmr spectra, following 1.39 (the d of each peak ownership, 3H), 1.55 ~ 1.65 (m, 6H), 2.20-2.23 (m, 2H), 3.55 (t, 2H), 3.84 (t, 4H), 3.96 (q, 1H), 4.95 (t, 1H), product structure formula is as follows:
。
Embodiment 4
(1) synthesis (n=4) of intermediate II: add 360Kg (3.46Kmol) D-ALPHA-Hydroxypropionic acid methyl esters in the reactor of 1000L, logical nitrogen protection, drip 343Kg azepan (1.0eq), stirring reaction 8h under 60 ° of C, concentrate most of by-product carbinol in reaction solution, add 17Kg azepan (0.05eq), nitrogen protection, reaction 5h is continued under 60 ° of C, reaction solution is concentrated, obtain orange-yellow oily liquids (D)-1-(1-azo-cycle heptane base)-2-hydroxyl-1-acetone 390Kg (theoretical yield 578Kg), yield is 67.47%, product is dissolved in deuterochloroform, characterized by proton nmr spectra, each peak ownership is as follows, 1.39 (d, 3H), 1.50-1.53 (m, 8H), 3.34 (t, 4H), 4.34 (q, 1H), product structure formula is as follows:
。
(2) preparation (n=4) of chemical compounds I: 300Kg the first step product (D)-1-(1-azo-cycle heptane base)-2-hydroxyl-1-acetone is joined in the reactor of 1000L, add 500L tetrahydrofuran (THF), pass into nitrogen protection, add tosic acid 30Kg (0.1eq) in batches, temperature is not more than 0 ° of C, then 3 of 162Kg are dripped, 4-dihydropyrane (1.1eq), control temperature is no more than 20 ° of C, drip off rear 25 ° of C reaction, monitoring reaction after 5h, after question response is complete, with the Na of 12% 2cO 3(300Kg) aqueous solution cancellation reaction, leave standstill 30min separatory, the tertiary fourth methyl ether back extraction of water layer 200L, merge organic layer, salt solution 200Kg with 15% washs once, organic layer 20Kg anhydrous sodium sulfate drying 2h, filter, filtrate obtains 230Kg pale yellowish oil (D)-1-(1-azepan base)-2-(2-THP trtrahydropyranyl) oxygen-1-acetone at 30 ~ 55 ° of C decompression precipitations, yield is 51.41%, product is dissolved in deuterochloroform, characterized by proton nmr spectra, following 1.39 (the d of each peak ownership, 3H), 1.50-1.53 (m, 8H), 1.55 ~ 1.65 (m, 6H), 3.34 (t, 4H), 3.55 (t, 2H), 3.96 (q, 1H), , 4.95 (t, 1H), product structure formula is as follows:
。
Embodiment 5
(1) synthesis (n=5) of intermediate II: add 360Kg (3.46Kmol) D-ALPHA-Hydroxypropionic acid methyl esters in the reactor of 1000L, logical nitrogen protection, drip 391Kg Azacyclooctane (1.0eq), stirring reaction 8h under 60 ° of C, concentrate most of by-product carbinol in reaction solution, add 19.6Kg Azacyclooctane (0.05eq), nitrogen protection, reaction 5h is continued under 60 ° of C, reaction solution is concentrated, obtain orange-yellow oily liquids (D)-1-(1-azo-cycle octyl)-2-hydroxyl-1-acetone 410Kg (theoretical yield 640Kg), yield is 64.06%, product is dissolved in deuterochloroform, characterized by proton nmr spectra, following 1.39 (the d of each peak ownership, 3H), 1.45-1.55 (m, 10H), 3.34 (t, 4H), 4.34 (q, 1H), product structure formula is as follows:
。
(2) preparation (n=5) of chemical compounds I: 400Kg the first step product (D)-1-(1-azo-cycle octyl)-2-hydroxyl-1-acetone is joined in the reactor of 1000L, add 800L tetrahydrofuran (THF), pass into nitrogen protection, add tosic acid 37.2Kg (0.1eq) in batches, temperature is not more than 0 ° of C, then 3 of 200Kg are dripped, 4-dihydropyrane (1.1eq), control temperature is no more than 20 ° of C, drip off rear 25 ° of C reaction, monitoring reaction after 5h, after question response is complete, with the Na of 12% 2cO 3(400Kg) aqueous solution cancellation reaction, leave standstill 30min separatory, the tertiary fourth methyl ether back extraction of water layer 300L, merge organic layer, salt solution 300Kg with 15% washs once, organic layer 30Kg anhydrous sodium sulfate drying 2h, filter, filtrate obtains 290Kg yellow oily (D)-1-(1-Azacyclooctane base)-2-(2-THP trtrahydropyranyl) oxygen-1-acetone at 30 ~ 55 ° of C decompression precipitations, yield is 50.05%, product is dissolved in deuterochloroform, characterized by proton nmr spectra, following 1.39 (the d of each peak ownership, 3H), 1.30-1.32 (m, 6H), 1.52-1.55 (m, 4H), 1.62-1.86 (m, 8H), 3.20 (t, 2H), 3.55 (t, 2H), 3.96 (q, 1H), 4.95 (t, 1H), .Product structure formula is as follows:
。

Claims (9)

1.一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物，其特征在于，该化合物结构通式如下： 1. a triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl) oxygen-1-acetone compound, characterized in that, the The general structural formula of the compound is as follows: 其中，n=1~5。 Among them, n=1~5. 2.根据权利要求1所述的一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物的制备方法，其特征在于，包括以下步骤：（1）N2保护下，D-乳酸甲酯与环烷仲胺在30~60°C下以环烷仲胺作为溶剂（n=1~5）反应，制得关键中间体Ⅱ，其中，D-乳酸甲酯与环烷仲胺的摩尔比为1:1~1:1.3，（2）N2保护下，中间体Ⅱ溶于有机溶剂中，与3,4-二氢吡喃以有机强酸作为催化剂，室温反应，制得化合物Ⅰ，其中n=1~5，中间体Ⅱ与催化剂的摩尔比为1：0.05~0.1，中间体Ⅱ与3,4-二氢吡喃的摩尔比为1:1~1:1.4，反应式如下： 2. A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl)oxy-1-acetones according to claim 1 The preparation method of the compound is characterized in that it comprises the following steps: (1) Under the protection of N 2 , methyl D-lactate and naphthenic secondary amine are used as solvent (n=1~ 5) Reaction to obtain the key intermediate II, wherein the molar ratio of D-methyl lactate to secondary naphthenic amine is 1:1~1:1.3, (2) Under the protection of N2 , the intermediate II is dissolved in an organic solvent , react with 3,4-dihydropyran with strong organic acid as a catalyst at room temperature to obtain compound I, wherein n=1~5, the molar ratio of intermediate II to catalyst is 1:0.05~0.1, intermediate II The molar ratio to 3,4-dihydropyran is 1:1~1:1.4, and the reaction formula is as follows: 。 . 3.根据权利要求2所述的一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物的制备方法，其特征在于，所述环烷仲胺为四氢吡咯。 3. A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl) oxygen-1-acetones according to claim 2 The preparation method of the compound is characterized in that the secondary cycloalkane amine is tetrahydropyrrole. 4.根据权利要求2或3所述的一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物的制备方法，其特征在于，步骤（1）的反应温度为40~50°C。 4. A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl) oxygen-1-according to claim 2 or 3 The preparation method of acetone compound is characterized in that the reaction temperature of step (1) is 40-50°C. 5.根据权利要求2或3所述的一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物的制备方法，其特征在于，步骤（1）中D-乳酸甲酯与环烷仲胺的摩尔比为1:1.05。 5. A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl) oxygen-1-according to claim 2 or 3 The preparation method of acetone compound is characterized in that the molar ratio of methyl D-lactate to secondary naphthenic amine in step (1) is 1:1.05. 6.根据权利要求2或3所述的一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物的制备方法，其特征在于，步骤（2）中，所述有机强酸为对甲苯磺酸或者甲磺酸，所述有机溶剂为四氢呋喃。 6. A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl) oxygen-1-according to claim 2 or 3 The preparation method of acetone compounds is characterized in that, in step (2), the strong organic acid is p-toluenesulfonic acid or methanesulfonic acid, and the organic solvent is tetrahydrofuran. 7.根据权利要求2或3所述的一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物的制备方法，其特征在于，步骤（2）中，中间体Ⅱ与催化剂的摩尔比为1：0.1。 7. A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl) oxygen-1-according to claim 2 or 3 The preparation method of acetone compounds is characterized in that, in step (2), the molar ratio of intermediate II to catalyst is 1:0.1. 8.根据权利要求2或3所述的一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物的制备方法，其特征在于，步骤（2）中，中间体Ⅱ与3,4-二氢吡喃的摩尔比为1:1.1。 8. A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl) oxygen-1-according to claim 2 or 3 The preparation method of acetone compounds is characterized in that, in step (2), the molar ratio of intermediate II to 3,4-dihydropyran is 1:1.1. 9.根据权利要求2或3所述的一种三唑类药物中间体(D)-1-(1-环烷仲胺基)-2-(2-四氢吡喃基)氧-1-丙酮类化合物的制备方法，其特征在于，步骤（2）中，滴加催化剂时反应温度不超过0°C，滴加3,4-二氢吡喃时反应温度不超过20°C。 9. A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl) oxygen-1-according to claim 2 or 3 The method for preparing acetone compounds is characterized in that in step (2), the reaction temperature does not exceed 0°C when the catalyst is added dropwise, and the reaction temperature does not exceed 20°C when the 3,4-dihydropyran is added dropwise.
CN201510758692.0A 2015-11-10 2015-11-10 A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl)oxy-1-acetone compound and its synthesis method Pending CN105367528A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510758692.0A CN105367528A (en) 2015-11-10 2015-11-10 A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl)oxy-1-acetone compound and its synthesis method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510758692.0A CN105367528A (en) 2015-11-10 2015-11-10 A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl)oxy-1-acetone compound and its synthesis method

Publications (1)

Publication Number Publication Date
CN105367528A true CN105367528A (en) 2016-03-02

Family

ID=55370216

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510758692.0A Pending CN105367528A (en) 2015-11-10 2015-11-10 A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl)oxy-1-acetone compound and its synthesis method

Country Status (1)

Country Link
CN (1) CN105367528A (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0421210A2 (en) * 1989-09-26 1991-04-10 Takeda Chemical Industries, Ltd. Triazole compounds, their production and use
US6133485A (en) * 1998-04-15 2000-10-17 Synphar Laboratories, Inc. Asymmetric synthesis of 2-(2,4-difluorophenyl)-1-heterocycl-1-yl butan-2,3-diols
US6300353B1 (en) * 1998-03-06 2001-10-09 Basilea Pharmaceutica Ag, A Swiss Company Azoles for treatment of fungal infections
CN101321522A (en) * 2005-12-01 2008-12-10 巴斯利尔药物股份公司 The preparation method of epoxy butanol intermediate

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0421210A2 (en) * 1989-09-26 1991-04-10 Takeda Chemical Industries, Ltd. Triazole compounds, their production and use
US6300353B1 (en) * 1998-03-06 2001-10-09 Basilea Pharmaceutica Ag, A Swiss Company Azoles for treatment of fungal infections
US6133485A (en) * 1998-04-15 2000-10-17 Synphar Laboratories, Inc. Asymmetric synthesis of 2-(2,4-difluorophenyl)-1-heterocycl-1-yl butan-2,3-diols
CN101321522A (en) * 2005-12-01 2008-12-10 巴斯利尔药物股份公司 The preparation method of epoxy butanol intermediate

Similar Documents

Publication Publication Date Title
DK2970263T3 (en) PROCESSES FOR THE MANUFACTURE OF AN APOPTOSIS-PRACTICING EFFECT
EP2562152B1 (en) A method for preparing 2,5-dimethylphenylacetic acid
MX2010014224A (en) A process for the preparation of the apoptosis promoter abt-263.
Huang et al. Asymmetric copper-catalyzed propargylic amination with amine hydrochloride salts
CN109020924B (en) A kind of method of benzenesulfonyl chloride compound and secondary amine metal-free catalysis synthesis of benzenesulfonamide compound
CN102336735A (en) Method for preparing cyclic carbonate by catalyzing with ionic liquid
CN113277963B (en) A kind of amine compound and its preparation method and application
CN104844491B (en) A kind of synthetic method of dithiocarbamate
CN104672121B (en) The preparation method of 2R (2,5 difluorophenyl) pyrrolidine hydrochloride
JP6064264B2 (en) Catalytic synthesis of vitamin A intermediate
CN105367556A (en) A kind of synthetic method of antifungal drug intermediate (2R,3S)-1-(1,2,4-triazolyl)-2-difluorophenyl-2,3-epoxybutane
CN105367528A (en) A kind of triazole drug intermediate (D)-1-(1-cycloalkane secondary amino)-2-(2-tetrahydropyranyl)oxy-1-acetone compound and its synthesis method
DE602006020196D1 (en) PROCESS FOR PREPARING A 3-O-ALKYLASCORBIC ACID
CN104031086B (en) Method for synthesizing alpha-amino alkyl phosphonate compounds
CN104402890A (en) Preparation method of penoxsulam
EP3495341B1 (en) Preparation process of perfluoroalkyl compound with monohydroperfluoroalkane as starting material
CN106795070A (en) Method for preparing halogeno-benzene
CN109503578A (en) 1-Oxyidene-2,8-diazaspiro[4.5]decane-4-carboxylic acid ethyl ester-8-carboxylic acid tert-butyl ester
CN105237486B (en) The synthetic method of the dimethyl pyrazine of 2 ethyl 3,6
CN109232350A (en) A method of preparing N-Boc-3- pyrrolidine formaldehyde
CN105439875A (en) Synthesis method for compound tulobuterol
CN115215803B (en) Preparation method of 4-halogenated-1- (difluoromethyl) -1H-imidazole
CN105085526B (en) A kind of improved silaenafil preparation method
JP4879907B2 (en) Process for producing phenyl 2-pyrimidinyl ketones and novel intermediates thereof
KR101453413B1 (en) Method for preparation of alpha-carboline derivatives

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20160302

RJ01 Rejection of invention patent application after publication