4-bromo-2-thiophenecarbonitrile -Drug Synthesis Database

【结构式】

【分子编号】58339

【品名】4-bromo-2-thiophenecarbonitrile

【CA登记号】

【分子式】C₅H₂BrNS

【分子量】188.04762

【元素组成】C 31.94% H 1.07% Br 42.49% N 7.45% S 17.05%

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：(VI)

Addition of methylmagnesium bromide to methyl 2-amino-5-bromobenzoate (I) provides the tertiary alcohol (II). Subsequent ring closure of the amino carbinol (II) with acetaldehyde leads to the benzoxazine (III). Treatment of the bromobenzoxazine (III) with bis(pinacolato)diboron (IV) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) chloride furnishes the aryl borate (V). This is finally subjected to Suzuki coupling with 5-bromo-2-thiophenecarbonitrile (VI) to produce the title benzoxazinyl thiophene derivative.

参考文献中间体

合成目标

【1】 Zhang, P.; et al.; Potent nonsteroidal progesterone receptor agonists: Synthesis and SAR study of 6-aryl benzoxazines. Bioorg Med Chem Lett 2002, 12, 5, 787.
【2】 Jones, T.K.; Zhi, L.; Tegley, C.M.; Fensome, A.; Zhang, P.; Terefenko, E.A.; Marschke, K.B. (Ligand Pharmaceuticals, Inc.; Wyeth); Quinazolinone and benzoxazine derivs. as progesterone receptor modulators. EP 1175404; WO 0066560 .
【3】 Jones, T.K.; Zhi, L.; Tegley, C.M.; Marschke, K.B.; Grubb, G.S. (Ligand Pharmaceuticals, Inc.; Wyeth); Contraceptive compsns. containing quinazolinone and benzoxazine derivs.. WO 0066164; WO 0066165 .

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)	58335	methyl 2-amino-5-bromobenzoate		C₈H₈BrNO₂	详情	详情
(II)	58336	2-(2-amino-5-bromophenyl)-2-propanol		C₉H₁₂BrNO	详情	详情
(III)	58337	6-bromo-2,4,4-trimethyl-1,4-dihydro-2H-3,1-benzoxazine		C₁₁H₁₄BrNO	详情	详情
(IV)	53342	4,4,4',4',5,5,5',5'-Octamethyl-2,2'-bi-1,3,2-dioxaborolane; Bis(pinacolato)diboron; Diboron pinacol ester	73183-34-3	C₁₂H₂₄B₂O₄	详情	详情
(V)	58338	2,4,4-trimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dihydro-2H-3,1-benzoxazine		C₁₇H₂₆BNO₃	详情	详情
(VI)	58339	4-bromo-2-thiophenecarbonitrile		C₅H₂BrNS	详情	详情

Extended Information