(3R,4R)-4-bromo-2,2-dimethyl-6-(2-methyl-4-pyridinyl)-3,4-dihydro-2H-chromen-3-ol -Drug Synthesis Database

【结构式】

【分子编号】50059

【品名】(3R,4R)-4-bromo-2,2-dimethyl-6-(2-methyl-4-pyridinyl)-3,4-dihydro-2H-chromen-3-ol

【CA登记号】

【分子式】C₁₇H₁₈BrNO₂

【分子量】348.23946

【元素组成】C 58.63% H 5.21% Br 22.95% N 4.02% O 9.19%

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：(XIII)

Electrophilic bromination of chromene (XII) with N-bromosuccinimide in moist DMSO produced the trans-bromohydrin (XIII). The racemic (XIII) was then resolved by esterification with (R)-alpha-methoxyphenylacetic acid (XIV), using DCC as the coupling reagent, and subsequent chromatographic separation of the diastereomeric mixture. Hydrolysis of the desired bromoester isomer (XV) under basic conditions gave rise to the chiral cis-epoxide (XVI). The target amino alcohol (XVII) was then obtained by regioselective ring opening of epoxide (XVI) with ethanolic ammonia in a pressure vessel. Finally, coupling of (XVII) with nicotinoyl chloride (XVIII) furnished the title amide.

参考文献中间体

合成目标

【1】 Manley, P.W. (Novartis AG; Novartis Deutschland GmbH); 2,2-Dialkyl- and 2,2-dialkyl-3, 4-dihydro-3-hydroxy-2H-1-benzopyrans, their use as pharmaceuticals. EP 0623129; WO 9412493 .
【2】 Manley, P.W. (Novartis AG); 2,2-Dialkyl- and 2,2-dialkyl-3, 4-dihydro-3-hydroxy-2H-1-benzopyrans. US 5574049 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	50058	4-(2,2-dimethyl-2H-chromen-6-yl)-2-methylpyridine		C₁₇H₁₇NO	详情	详情
(XIII)	50059	(3R,4R)-4-bromo-2,2-dimethyl-6-(2-methyl-4-pyridinyl)-3,4-dihydro-2H-chromen-3-ol		C₁₇H₁₈BrNO₂	详情	详情
(XIV)	50060	(2R)-2-methoxy-2-phenylethanoic acid	3966-32-3	C₉H₁₀O₃	详情	详情
(XV)	50061	(3R,4R)-4-bromo-2,2-dimethyl-6-(2-methyl-4-pyridinyl)-3,4-dihydro-2H-chromen-3-yl (2R)-2-methoxy-2-phenylethanoate		C₂₆H₂₆BrNO₄	详情	详情
(XVI)	50062	4-[(1aS,7bS)-2,2-dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl]-2-methylpyridine		C₁₇H₁₇NO₂	详情	详情
(XVII)	50063	(3S,4R)-4-amino-2,2-dimethyl-6-(2-methyl-4-pyridinyl)-3,4-dihydro-2H-chromen-3-ol		C₁₇H₂₀N₂O₂	详情	详情
(XVIII)	10753	Nicotinoyl chloride		C₆H₄ClNO	详情	详情

Extended Information