2-bromo-N,N-dimethylacetamide -Drug Synthesis Database

【结构式】

【分子编号】29753

【品名】2-bromo-N,N-dimethylacetamide

【CA登记号】

【分子式】C₄H₈BrNO

【分子量】166.01766

【元素组成】C 28.94% H 4.86% Br 48.13% N 8.44% O 9.64%

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：(II)

The reaction of p-hydrophenylacetic acid (I) with N,N-dimethylbromoacetamide (II) by means of triethylamine in reftuxing acetonitrile gives N,N-dimethylcarbamoylmethyl-p-hydroxyphenylacetate (III), which is then condensed with p-guanidinobenzoyl chloride (IV) [obtained from the corresponding acid p-guanidinobenzoic acid (V) and thionyl chloride] in pyridine.

参考文献中间体

合成目标

【1】 Fujii, S.; Uegai, Y.; Watanabe, T.; Kayama, N. (Ono Pharmaceutical Co., Ltd.); Guanidinobenzoic acid derivatives. DE 2548886; FR 2289181; GB 1472700; JP 76054530; US 4021472 .
【2】 Fujii, S.; et al. (Ono Pharmaceutical Co., Ltd.); Guanidinobenzoic acid derivatives and antiplasmin agents and remedies for pancreas diseases containing the said guanidinobensolc acid derivatives. JP 52089640 .
【3】 Castaner, J.; Serradell, M.N.; Hashimoto, K.; Camostat Mesylate. Drugs Fut 1985, 10, 11, 897.

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)	18430	2-(4-Hydroxyphenyl)acetic acid; 4-Hydroxyphenylacetic acid	156-38-7	C₈H₈O₃	详情	详情
(II)	29753	2-bromo-N,N-dimethylacetamide		C₄H₈BrNO	详情	详情
(III)	29754	2-(dimethylamino)-2-oxoethyl 2-(4-hydroxyphenyl)acetate		C₁₂H₁₅NO₄	详情	详情
(IV)	29755	4-[[amino(imino)methyl]amino]benzoic acid		C₈H₉N₃O₂	详情	详情
(V)	22548	4-[[amino(imino)methyl]amino]benzoyl chloride		C₈H₈ClN₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

The benzyl-protected 2-(2-hydroxyethyl)phenol (I) was brominated in HOAc to give (II). Lithiation of aryl bromide (II) followed by in situ condensation of the resulting organolithium derivative (III) with diethyl oxalate under -95 C furnished the keto ester (IV). Subsequent ketone reduction by NaBH4 afforded hydroxy ester (V), which was further hydrolyzed to the mandelic acid derivative (VI). The condensation of racemic acid (VI) with (S)-2-amino-7-hydroxytetraline (VII) gave rise to a diastereomeric mixture of hydroxy amides from which the desired (S,R)-diastereoisomer (VIII) was isolated by column chromatography. Reduction of the amide function of (VIII) using borane-dimethyl sulfide complex yielded the amino alcohol (IX). Alkylation of the phenolic hydroxyl group of (IX) with 2-bromo-N,N-dimethylacetamide (X) provided the corresponding (aryloxy)acetamide (XI). Then, hydrogenolysis of the benzyl protecting groups over Pd/C furnished the target compound, which was finally isolated as the corresponding sulfate salt.

参考文献中间体

合成目标

【1】 Kitazawa, M.; Okazaki, K.; Tamai, T.; Saito, M.; Muranaka, H.; Tanaka, N.; Kobayahi, H.; Kikuchi, K. (Kissei Pharmaceutical Co., Ltd.); 3,4-Disubstd. phenylethanolaminotetralincarboxamide derivs.. EP 0882704; US 6133266; WO 9730023 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	50674	1-(benzyloxy)-2-[2-(benzyloxy)ethyl]benzene; benzyl 2-[2-(benzyloxy)ethyl]phenyl ether	C₂₂H₂₂O₂	详情	详情
(II)	50675	benzyl 2-(benzyloxy)-5-bromophenethyl ether; 1-(benzyloxy)-2-[2-(benzyloxy)ethyl]-4-bromobenzene	C₂₂H₂₁BrO₂	详情	详情
(III)	50676	[4-(benzyloxy)-3-[2-(benzyloxy)ethyl]phenyl]lithium	C₂₂H₂₁LiO₂	详情	详情
(IV)	50677	ethyl 2-[4-(benzyloxy)-3-[2-(benzyloxy)ethyl]phenyl]-2-oxoacetate	C₂₆H₂₆O₅	详情	详情
(V)	50678	ethyl 2-[4-(benzyloxy)-3-[2-(benzyloxy)ethyl]phenyl]-2-hydroxyacetate	C₂₆H₂₈O₅	详情	详情
(VI)	50679	2-[4-(benzyloxy)-3-[2-(benzyloxy)ethyl]phenyl]-2-hydroxyacetic acid	C₂₄H₂₄O₅	详情	详情
(VII)	32819	(7S)-7-amino-5,6,7,8-tetrahydro-2-naphthalenol	C₁₀H₁₃NO	详情	详情
(VIII)	50680	(2R)-2-[4-(benzyloxy)-3-[2-(benzyloxy)ethyl]phenyl]-2-hydroxy-N-[(2S)-7-hydroxy-1,2,3,4-tetrahydro-2-naphthalenyl]ethanamide	C₃₄H₃₅NO₅	详情	详情
(IX)	50681	(7S)-7-[((2R)-2-[4-(benzyloxy)-3-[2-(benzyloxy)ethyl]phenyl]-2-hydroxyethyl)amino]-5,6,7,8-tetrahydro-2-naphthalenol	C₃₄H₃₇NO₄	详情	详情
(X)	29753	2-bromo-N,N-dimethylacetamide	C₄H₈BrNO	详情	详情
(XI)	50682	2-([(7S)-7-[((2R)-2-[4-(benzyloxy)-3-[2-(benzyloxy)ethyl]phenyl]-2-hydroxyethyl)amino]-5,6,7,8-tetrahydro-2-naphthalenyl]oxy)-N,N-dimethylacetamide	C₃₈H₄₄N₂O₅	详情	详情

Extended Information