3-methoxy-4-(1-pyrrolidinylmethyl)benzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】31414

【品名】3-methoxy-4-(1-pyrrolidinylmethyl)benzoyl chloride

【CA登记号】

【分子式】C₁₃H₁₆ClNO₂

【分子量】253.72828

【元素组成】C 61.54% H 6.36% Cl 13.97% N 5.52% O 12.61%

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：(V)

Radical bromination of methyl 3-methoxy-4-methylbenzoate (I) using N-bromosuccinimide and azobisisobutyronitrile gave benzyl bromide (II), which was treated with pyrrolidine to afford the tertiary amine (III). Hydrolysis of the methyl ester group of (III) with LiOH provided carboxylic acid (IV), which was converted to acid chloride (V) upon treatment with SOCl2.

参考文献中间体

合成目标

【1】 Antithrombotic diamines. EP 0863755; US 6025382; WO 9725033 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(I)	11919	methyl 3-methoxy-4-methylbenzoate	3556-83-0	C₁₀H₁₂O₃	详情	详情
(II)	11920	methyl 4-(bromomethyl)-3-methoxybenzoate; 4-(Bromomethyl)-3-methoxy benzoic acid methyl ester		C₁₀H₁₁BrO₃	详情	详情
(III)	31412	methyl 3-methoxy-4-(1-pyrrolidinylmethyl)benzoate		C₁₄H₁₉NO₃	详情	详情
(IV)	31413	3-methoxy-4-(1-pyrrolidinylmethyl)benzoic acid		C₁₃H₁₇NO₃	详情	详情
(V)	31414	3-methoxy-4-(1-pyrrolidinylmethyl)benzoyl chloride		C₁₃H₁₆ClNO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Condensation of 4-benzyloxybenzaldehyde (VI) with N,N-dimethylthioformamide in the presence of LDA in THF at -78 C provided the alpha-hydroxythioacetamide (VII), which was cyclized with methanesulfonic acid to yield benzothiophene (VIII). Subsequent acylation of (VIII) with the intermediate acid chloride (V) in boiling chlorobenzene provided ketone (IX). 4-Bromophenol (X) was protected as the triisopropylsilyl ether using triisopropylsilyl trifluoromethanesulfonate and imidazole, and then converted to the corresponding Grignard reagent (XI) with Mg in THF. Displacement of the dimethylamino group from benzothiophene (IX) by Grignard reagent (XI) furnished the 2-arylbenzothiophene (XII), which was desilylated with tetrabutylammonium fluoride to give (XIII). The ketone function of (XIII) was then reduced by means of LiAlH4 to yield (XIV).

参考文献中间体

合成目标

【1】 Antithrombotic diamines. EP 0863755; US 6025382; WO 9725033 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	31414	3-methoxy-4-(1-pyrrolidinylmethyl)benzoyl chloride		C₁₃H₁₆ClNO₂	详情	详情
(VI)	29179	4-(Benzyloxy)benzaldehyde	4397-53-9	C₁₄H₁₂O₂	详情	详情
(VII)	29181	2-[4-(benzyloxy)phenyl]-2-hydroxy-N,N-dimethylethanethioamide		C₁₇H₁₉NO₂S	详情	详情
(VIII)	29182	6-(benzyloxy)-N,N-dimethyl-1-benzothiophen-2-amine		C₁₇H₁₇NOS	详情	详情
(IX)	31415	[6-(benzyloxy)-2-(dimethylamino)-1-benzothiophen-3-yl][3-methoxy-4-(1-pyrrolidinylmethyl)phenyl]methanone		C₃₀H₃₂N₂O₃S	详情	详情
(X)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(XI)	31416	bromo[4-[(triisopropylsilyl)oxy]phenyl]magnesium		C₁₅H₂₅BrMgOSi	详情	详情
(XII)	31417	(6-(benzyloxy)-2-[4-[(triisopropylsilyl)oxy]phenyl]-1-benzothiophen-3-yl)[3-methoxy-4-(1-pyrrolidinylmethyl)phenyl]methanone		C₄₃H₅₁NO₄SSi	详情	详情
(XIII)	31418	[6-(benzyloxy)-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl][3-methoxy-4-(1-pyrrolidinylmethyl)phenyl]methanone		C₃₄H₃₁NO₄S	详情	详情
(XIV)	31419	4-[6-(benzyloxy)-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]-1-benzothiophen-2-yl]phenol		C₃₄H₃₃NO₃S	详情	详情

Extended Information