(3aR,9bS)-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole-8-carbonitrile -Drug Synthesis Database

【结构式】

【分子编号】33765

【品名】(3aR,9bS)-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole-8-carbonitrile

【CA登记号】

【分子式】C₁₂H₁₂N₂O

【分子量】200.24016

【元素组成】C 71.98% H 6.04% N 13.99% O 7.99%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

Reduction of the ester function of trans pyrrolidine (I) with LiAlH4 gave alcohol (II). Subsequent cleavage of the methyl ether of (II) using EtSNa in hot DMF furnished diol (III), which was submitted to ring closure under Mitsunobu conditions, yielding chromene (IV). The 8-cyano group was introduced by displacement of the bromine of (IV) by means of Zn(CN)2 and Pd(PPh3)4 in DMF. The resulting nitrile (V) was N-debenzylated by hydrogenolysis over Pd/C to provide intermediate (VI).

参考文献中间体

合成目标

【1】 Audinot, V.; Dubuffet, T.; Newman-Tancredi, A.; Cussac, D.; Millan, M.J.; Lavielle, G.; Loutz, A.; Novel benzopyrano[3,4-c]pyrrole derivatives as potent and selective dopamine D3 receptor antagonists. Bioorg Med Chem Lett 1999, 9, 14, 2059.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	33760	methyl (3R,4S)-1-benzyl-4-(5-bromo-2-methoxyphenyl)-3-pyrrolidinecarboxylate	C₂₀H₂₂BrNO₃	详情	详情
(II)	33761	[(3R,4S)-1-benzyl-4-(5-bromo-2-methoxyphenyl)pyrrolidinyl]methanol	C₁₉H₂₂BrNO₂	详情	详情
(III)	33762	2-[(3S,4R)-1-benzyl-4-(hydroxymethyl)pyrrolidinyl]-4-bromophenol	C₁₈H₂₀BrNO₂	详情	详情
(IV)	33763	(3aR,9bS)-2-benzyl-8-bromo-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole	C₁₈H₁₈BrNO	详情	详情
(V)	33764	(3aR,9bS)-2-benzyl-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole-8-carbonitrile	C₁₉H₁₈N₂O	详情	详情
(VI)	33765	(3aR,9bS)-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole-8-carbonitrile	C₁₂H₁₂N₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Coupling of 4-aminobutanol (VII) with 4-phenylbenzoyl chloride (VIII) produced hydroxy amide (IX). Further Swern oxidation of the alcohol group of (IX) using oxalyl chloride and DMSO afforded aldehyde (X). Finally, reductive condensation of aldehyde (X) with pyrrolidine (VI) in the presence of NaBH(OAc)3 afforded the title compound.

参考文献中间体

合成目标

【1】 Audinot, V.; Dubuffet, T.; Newman-Tancredi, A.; Cussac, D.; Millan, M.J.; Lavielle, G.; Loutz, A.; Novel benzopyrano[3,4-c]pyrrole derivatives as potent and selective dopamine D3 receptor antagonists. Bioorg Med Chem Lett 1999, 9, 14, 2059.
【2】 Lejeune, F.; Hautefaye, P.; Millan, M.; Dubuffet, T.; Lavielle, G. (ADIR et Cie.); Chromene derivs., process for their preparation and pharmaceutical compsns. containing them. EP 0887350; JP 1999071376; US 6090837 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	33765	(3aR,9bS)-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole-8-carbonitrile		C₁₂H₁₂N₂O	详情	详情
(VII)	33766	4-amino-1-butanol	13325-10-5	C₄H₁₁NO	详情	详情
(VIII)	28439	[1,1'-biphenyl]-4-carbonyl chloride	14002-51-8	C₁₃H₉ClO	详情	详情
(IX)	33767	N-(4-hydroxybutyl)[1,1'-biphenyl]-4-carboxamide		C₁₇H₁₉NO₂	详情	详情
(X)	33768	N-(4-oxobutyl)[1,1'-biphenyl]-4-carboxamide		C₁₇H₁₇NO₂	详情	详情

Extended Information