GB2055806A - Preparation of 2-isopropylamino- pyrimidine - Google Patents
Preparation of 2-isopropylamino- pyrimidine Download PDFInfo
- Publication number
- GB2055806A GB2055806A GB8019772A GB8019772A GB2055806A GB 2055806 A GB2055806 A GB 2055806A GB 8019772 A GB8019772 A GB 8019772A GB 8019772 A GB8019772 A GB 8019772A GB 2055806 A GB2055806 A GB 2055806A
- Authority
- GB
- United Kingdom
- Prior art keywords
- preparation
- isopropylamino
- pyrimidine
- sulphate
- tetraethoxy
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- FTCYIGBVOHNHCD-UHFFFAOYSA-N isaxonine Chemical compound CC(C)NC1=NC=CC=N1 FTCYIGBVOHNHCD-UHFFFAOYSA-N 0.000 title claims abstract description 8
- KVJHGPAAOUGYJX-UHFFFAOYSA-N 1,1,3,3-tetraethoxypropane Chemical compound CCOC(OCC)CC(OCC)OCC KVJHGPAAOUGYJX-UHFFFAOYSA-N 0.000 claims abstract description 6
- MFIQZHWDRVKGAK-UHFFFAOYSA-N 2-propan-2-ylguanidine;sulfuric acid Chemical compound OS(O)(=O)=O.CC(C)NC(N)=N.CC(C)NC(N)=N MFIQZHWDRVKGAK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 8
- 239000003929 acidic solution Substances 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 abstract description 2
- 239000007864 aqueous solution Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- BZZXQZOBAUXLHZ-UHFFFAOYSA-N (c-methylsulfanylcarbonimidoyl)azanium;sulfate Chemical compound CSC(N)=N.CSC(N)=N.OS(O)(=O)=O BZZXQZOBAUXLHZ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/48—Preparation of compounds having groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/30—Compounds having groups
- C07C43/303—Compounds having groups having acetal carbon atoms bound to acyclic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
2-Isopropylamino-pyrimidine, useful in the preparation of pharmaceuticals, is prepared by reacting bis(isopropylguanidine) sulphate with 1,1,3,3- tetraethoxy-propane in stoichiometric proportions at 40-60 DEG C in acidic aqueous solution.
Description
SPECIFICATION
Preparation of 2-isopropylamino-pyrimidine
The invention relates to a process for the preparation of 2-isopropylamino-pyrimidine, a compound used in the preparation of pharmaceuticals.
Various routes are known for the preparation of 2-isopropylamino-pyrimidine, but none of them is very satisfactory in respect of yield and/or cost. We have now found a new process, which is easy to perform and gives very favourable yields.
The invention provides a process for the preparation of 2-isopropylamino-pyrimidine, the process comprising reacting bis(isopropylguanidine)sulphate with 1,1 ,3,3-tetraethoxy-propane in stoichiometric proportions at 40-60"C, in acidic aqueous solution.
The 1,1 ,3,3-tetraethoxy-propane may be prepared by reacting a stoichiometric excess of triethylorthoformate with vinyl acetate at 70-90 C in the presence of ferric chloride and of acetic anhydride; the bis(isopropylguanidine)sulphate may be obtained by reaction of a stoichiometric excess of isopropylamine with bis(S-methylisothiourea)sulphate at reflux.
The invention is illustrated by the following Example.
EXAMPLE (1) Preparation of 1,1,3,3-tetraethoxy-propane
Into a one litre reactor fitted with warming, cooling and stirring means, there was poured, under nitrogen circulation, 25.8 g (0.3 mol) of vinyl acetate and 125.8 g (0.85 mol) of triethyl orthoformate. The mixture was heated to 70"C under stirring. There was then slowly added (over 3 hours) 1.4 g of ferric chloride and 2.2 g of acetic anhydride. At the end of the addition, stirring was maintained for half an hour and the mixture was then cooled; a black composition was obtained and this was extracted using 500 ml of diethyl ether. After washing and drying the extract, the diethyl ether was evacuated off, leading to an oily product boiling at 100-101"C under 15 mm of Hg. Yield 56.8 g (86%).
(2) Preparation of bisfisopropylguanidine)sulphate
Into a one litre reactor fitted with warming, cooling and stirring means were poured 108.5 g (0.39 mol) of bis(S-methylisothiourea)sulphate, 150 ml of water and 94 ml (or 68 ml, i.e. 1.15 mol) of isopropylamine. The mixture was refluxed for two hours and then evaporated to dryness. The residue was taken up in ethanol from which there was obtained, after filtration, washing and drying, 96 g (yield 82%) of product.
(3) Preparation of24soprop ylamino-p yrimidine
Into the same reactor as used in the previous step were poured 30 g (0.1 mol) of bis(isopropylguanidine)sulphate, 120 ml of water, 75 ml of pure hydrochloric acid solution (s.g. 1.18) and slowly (over 12 hours), at room temperature, 44 g (0.2 mol) of 1,1 ,3,3-tetraethoxy-propane. The mixture was then heated to 50-55"C under stirring for two hours, then cooled and neutralized by an excess of pure sodium hyroxide solution. The mixture was extracted using 300 ml of diethyl either. The extracts were washed with a saturated solution of sodium chloride, then dried and the diethyl ether was evacuated off. There was obtained 25 g (yield 91%) of a yellowish oil boiling at 91-91 .5 C under 11 mm of Hg, the analysis of which showed good correspondence with the formula C7H11N3.
Claims (2)
1. A process for the preparation of 2-isopropylamino-pyrimidine, the process comprising reacting bis(isopropylguanidine)sulphate with 1,1 ,3,3-tetraethoxy-propane in stoichiometric proportions at from 40"C to 600C in an aqueous acidic solution.
2. A process for the preparation of 2-isopropylamino-pyrimidine, the process being substantially as described herein with reference to the drawing.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8019772A GB2055806B (en) | 1979-08-09 | 1980-06-17 | Preparation of 2-isopropylaminopyrimidine |
| IT24038/80A IT1149842B (en) | 1979-08-09 | 1980-08-06 | PREPARATION OF 2-ISOPROPYLAMINOPYRIMIDINE |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7927811 | 1979-08-09 | ||
| GB8019772A GB2055806B (en) | 1979-08-09 | 1980-06-17 | Preparation of 2-isopropylaminopyrimidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2055806A true GB2055806A (en) | 1981-03-11 |
| GB2055806B GB2055806B (en) | 1983-03-02 |
Family
ID=26272492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8019772A Expired GB2055806B (en) | 1979-08-09 | 1980-06-17 | Preparation of 2-isopropylaminopyrimidine |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB2055806B (en) |
| IT (1) | IT1149842B (en) |
-
1980
- 1980-06-17 GB GB8019772A patent/GB2055806B/en not_active Expired
- 1980-08-06 IT IT24038/80A patent/IT1149842B/en active
Also Published As
| Publication number | Publication date |
|---|---|
| IT1149842B (en) | 1986-12-10 |
| IT8024038A0 (en) | 1980-08-06 |
| GB2055806B (en) | 1983-03-02 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |