US3293261A - 1-isopropyl-3-phenyl-5-aminopyrazole - Google Patents

Description

United States Eatent 6 "ice 3,293,261 I-ISOPROPYL-3-PI-ENYL-5-AM1NOPYRAZOLE Harry R. Snyder, Jrx, Norwich, N.Y., assignor to The Norwich Pharmacal Company, Norwich, N.Y., a corporation of New York No Drawing. Filed July 6, 1964, Ser. No. 380,681 1 Claim. (Cl. 260-310) This invention relates to pyrazole compounds, particularly those of the formula:

U-C 8H5 HzNiN N wherein R is a isopropyl or 2-hydroxyethyl group.

These new pyrazole compounds possess pharmocological activity being particularly distinguished by their ability to produce skeletal muscle relaxation upon administration to animals. Thus they are useful as muscle relaxants.

The compounds of Formula I are readily produced. They may :be simply prepared by bringing together benzoylacetonitrile and the appropriate hydrazine, preferably in the presence of a solvent. An illustrative reaction scheme is:

wherein R has the significance aforestated.

In carrying out the reaction the nitrile and the hydrazine are placed in an inert reaction solvent such as ethanol and the mixture preferably subjected to the influence of heat. Upon completion of the reaction the mixture is cooled and the precipitated solid recovered in conventional fashion. Recrystallization of the obtained product may be efiected in the usual manner. Suitable recrystallization media are the lower alkanols such as ethanol and methanol.

The compounds of this invention are readily formulated in a variety of pharmaceutical forms of the solid or liquid type using excipients and adjuvants with which incompatability is absent. Exemplary solid forms consist of magnesium stearate, sucrose, talc, stearic acid, agar pectin or acacia which may take the shape of tablets or powders. Exemplary liquid forms consist of peanut oil, olive oil, sesame oil and water. The liquid forms may be dispensed in capsules or as suspensions. In the case of veterinary application, the compounds may be placed in the feed or drinking water of animals.

3 ,293,261 Patented Dec. 20, 1966 In order that this invention may be readily available to and understood by those skilled in the art the following examples are appended:

EXAMPLE I (U-788) 1-is0pr0pyl-3-phenyl-5-aminopyrazole' Benzoylaoetonitrile (94 g., 0.65 mole) and isopropylhydrazine (48 g., 0.65 mole) are placed in a flask together with ethanol. The reaction mixture is refluxed for four hours. The alcohol is removed under reduced pressure to leave a syrupy residue which slowly crystallizes. The crude material is recrystallized from a minimum amount of methanol to yield 78 g. M.P. 93-95" C.

The material may be recrystallized again from methanol to yield 60 g., M.P. 95.5-96 C.

Analysis.Calcd for C H N C, 71.61; H, 7.51; N, 20.88. Found: C, 71.43; H, 7.65

EXAMPLE II (U-768) 1- (2-hydroxyethyl) -3-phenyZ-5-aminopyrazole Benzoylacetonitrile (290 g., 2.0 moles) and 2-hydr0xyethylhydrazine (152 g., 2.0 moles) are placed in a flask together with ethanol (1000 ml.). The mixture is refluxed for four hours, cooled, and filtered to yield 297 g. (73%) of product, M.P. 147.5149.5 C. Evaporation of the filtrate followed by recrystallization of the residue aflords another 28 g. of product; total yield is 325 g. This may be recrystallized from ethanol, M.P. 149150 C.

Analysis for C H N O.Calcd: C, 65.00; H, 6.45; N, 20.68. Found: C, 65.27; H, 6.52; N, 21.11.

What is claimed is:

1-isopr0pyl-3-phenyl-5-aminopyrazole.

7 References Cited by the Examiner UNITED STATES PATENTS 2,987,523 6/1961 Staub 260-4110 2,989,539 6/1961 Anderson 26031O 3,211,743 10/ 1965 Schmidt 2603 10 OTHER REFERENCES Alberti: Gaz. Chim. Italiana, vol. 89, pages 1017-32 (1959).

Searles et al.: Jour. Org. Chem., vol. 19, page 928 (1954 WALTER A. MODANCE, Primary Examiner.

N. TROUSOF, Assistant Examiner.