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【结 构 式】

【分子编号】43495

【品名】2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzoic acid

【CA登记号】

【 分 子 式 】C11H9ClN2O2

【 分 子 量 】236.65744

【元素组成】C 55.83% H 3.83% Cl 14.98% N 11.84% O 13.52%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(V)

Treatment of benzonitrile derivative (I) with 3-methylpyrazole (II) and NaH in DMF or KOtBu in THF yields a mixture of regioisomers from which compound (III) is obtained by recrystallization. Compound (III) is then converted into the corresponding benzamide (IV) by means of K2CO3 and H2O2 in DMSO. Hydrolysis of (IV) with aqueous H2SO4 and NaNO2 affords benzoic acid derivative (V), which is then condensed with benzodiazepine (VI) in the presence of DIEA by means of oxalyl chloride in CH2Cl2 and catalytic DMF. Alternatively (V) can be obtained by direct hydrolysis of (III) with NaOH in EtOH or by following this route: Condensation of methyl ester (VII) with 3-methyl pyrazole (II) by means of KH in DMF provides a mixture of regioisomers from which compound (VIII) is chromatographically separated and finally saponified by treatment with LiOH in THF or NaOH in acetonitrile.

1 Dusza, J.P.; Ashwell, M.A.; Caggiano, T.J.; et al.; VNA-932: First orally active, nonpeptide, vasopressin V2 receptor selective agonist. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 203.
2 Ashwell, M.A.; et al.; Synthesis and structure-activity relationships (SAR) of pyrrolobenzodiazepines related to the potent selective orally active nonpeptide vasopressin V2-receptor agonist VNA-932. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 202.
3 Trybulski, E.J.; Ashwell, M.A.; Molinari, A.J.; Bagli, J.F.; Chan, P.S.; Failli, A.A.; Dusza, J.P.; Albright, J.D.; Caggiano, T.J. (American Home Products Corp.); Tricyclic vasopressin agonists. EP 1000062; WO 9906409 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 43492 2-chloro-4-fluorobenzonitrile 60702-69-4 C7H3ClFN 详情 详情
(II) 37998 3-methyl-1H-pyrazole 1453-58-3 C4H6N2 详情 详情
(III) 43493 2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzonitrile C11H8ClN3 详情 详情
(IV) 43494 2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzamide C11H10ClN3O 详情 详情
(V) 43495 2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzoic acid C11H9ClN2O2 详情 详情
(VI) 21084 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine 22162-53-4 C12H12N2 详情 详情
(VII) 43496 methyl 2-chloro-4-fluorobenzoate 85953-29-3 C8H6ClFO2 详情 详情
(VIII) 43497 methyl 2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzoate C12H11ClN2O2 详情 详情
Extended Information