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【结 构 式】

【分子编号】38673

【品名】4'-chloro-N-[(2R)-2-hydroxy-2-phenylethyl][1,1'-biphenyl]-4-carboxamide

【CA登记号】

【 分 子 式 】C21H18ClNO2

【 分 子 量 】351.83216

【元素组成】C 71.69% H 5.16% Cl 10.08% N 3.98% O 9.09%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IX)

The reaction of bromobenzene (I) with 14CO2 by means of Mg in ether gives the corresponding benzoic acid (II), which is treated with SOCl2 and DMAP to yield the benzoyl chloride (III). The homologation of (III) with diazomethane in ether affords the phenacyl chloride (IV), which is enantioselectively reduced with borane and a chiral borolidine catalyst in THF to give (R)-2-chloro-1-phenylethanol (V). The cyclization of (V) by means of NaOH in ethyl ether yields the oxirane (VI), which by reaction with ammonia is converted into the (R)-2-amino-1-phenylethanol (VII). The condensation of (VII) with 4'-chlorobiphenyl-4-carboxylic acid (VIII) by means of CDI in DMF provides the amide (IX), which is cyclized to the oxazoline (X) by means of methanesulfonic anhydride and TEA in THF. Finally, this compound is condensed with imidazole (XI) by heating at 125 C.

1 Moenius, T.; et al.; C-14 labelling of NVPVID400 - a specific vitamin D-3-hydroxylase inhibitor. J Label Compd Radiopharm 1999, 42, 11, 1053.
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) 13365 Monobromobenzene; 1-Bromobenzene;Phenylbromide;bromobenzene 108-86-1 C6H5Br 详情 详情
(II) 10202 Benzoic acid 65-85-0 C7H6O2 详情 详情
(III) 10463 Benzoyl chloride 98-88-4 C7H5ClO 详情 详情
(IV) 38669 2-chloro-1-phenyl-1-ethanone 532-27-4 C8H7ClO 详情 详情
(V) 38670 (1R)-2-chloro-1-phenyl-1-ethanol 1674-30-2 C8H9ClO 详情 详情
(VI) 38671 (2R)-2-phenyloxirane C8H8O 详情 详情
(VII) 10173 (1R)-2-Amino-1-phenyl-1-ethanol 2549-14-6 C8H11NO 详情 详情
(VIII) 38672 4'-chloro[1,1'-biphenyl]-4-carboxylic acid C13H9ClO2 详情 详情
(IX) 38673 4'-chloro-N-[(2R)-2-hydroxy-2-phenylethyl][1,1'-biphenyl]-4-carboxamide C21H18ClNO2 详情 详情
(X) 38674 (5S)-2-(4'-chloro[1,1'-biphenyl]-4-yl)-5-phenyl-4,5-dihydro-1,3-oxazole C21H16ClNO 详情 详情
(XI) 10255 Imidazole; 1H-Imidazole 288-32-4 C3H4N2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

The reaction of (R)-2-phenyloxirane (I) with ammonia in ethanol gives 2-amino-1(R)-phenylethanol (II), which is condensed with 4'-chlorobiphenyl-4-carboxylic acid (III) by means of isobutyl chloroformate and TEA in DMF yielding the amide (IV). The cyclization of (IV) by means of methanesulfonic anhydride in pyridine affords the oxazoline (V), which is finally condensed with imidazole by heating at 120 C.

1 Schuster, I.; Egger, H. (Novartis AG; Novartis Deutschland GmbH); Acylated aminoalkanimidazoles and -triazoles. CA 2149459; EP 0683156; JP 1996053422; US 5622982 .
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) 38671 (2R)-2-phenyloxirane C8H8O 详情 详情
(II) 10173 (1R)-2-Amino-1-phenyl-1-ethanol 2549-14-6 C8H11NO 详情 详情
(III) 38672 4'-chloro[1,1'-biphenyl]-4-carboxylic acid C13H9ClO2 详情 详情
(IV) 38673 4'-chloro-N-[(2R)-2-hydroxy-2-phenylethyl][1,1'-biphenyl]-4-carboxamide C21H18ClNO2 详情 详情
(V) 38674 (5S)-2-(4'-chloro[1,1'-biphenyl]-4-yl)-5-phenyl-4,5-dihydro-1,3-oxazole C21H16ClNO 详情 详情
(VI) 10255 Imidazole; 1H-Imidazole 288-32-4 C3H4N2 详情 详情
Extended Information