N,N'-Dimethylcarbamoyl chloride; Dimethylcarbamoyl chloride; [(Chlorocarbonyl)(methyl)amino]methane -Drug Synthesis Database

【结构式】

【分子编号】13708

【品名】N,N'-Dimethylcarbamoyl chloride; Dimethylcarbamoyl chloride; [(Chlorocarbonyl)(methyl)amino]methane

【CA登记号】79-44-7

【分子式】C₃H₆ClNO

【分子量】107.53948

【元素组成】C 33.51% H 5.62% Cl 32.97% N 13.02% O 14.88%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The reaction of 3,5-dihydroxyacetophenone (I) with N,N-dimethylcarbamoyl chloride (II) in hot pyridine gives 3,5-bis(N,N-dimethylcarbamoyloxy) acetophenone (III), which is brominated with Br2 in dioxane yielding 3,5-bis(N,N-dimethylcarbamoyloxy)phenacyl bromide (IV). The condensation of (IV) with N benzyl-tert butylamine (V) in refluxing acetone affords the corresponding w-amino derivative (VI), which is finally hydrogenated with H2 over Pd/C in ethanol.

参考文献中间体

合成目标

【1】 Olsson, O.A.T.; Svensson, L.A.; Wetterlin, K.I.L. (Draco Lakemedel AB); Bronchospamolytic carbamate derivatives. DD 202001; EP 0043807; JP 8240453; US 4419364; US 4451663 .
【2】 Castaner, J.; Prous, J.; Bambuterol. Drugs Fut 1986, 11, 7, 553.

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)	24696	1-(3,5-dihydroxyphenyl)-1-ethanone	51863-60-6	C₈H₈O₃	详情	详情
(II)	13708	N,N'-Dimethylcarbamoyl chloride; Dimethylcarbamoyl chloride; [(Chlorocarbonyl)(methyl)amino]methane	79-44-7	C₃H₆ClNO	详情	详情
(III)	24698	3-acetyl-5-[[(dimethylamino)carbonyl]oxy]phenyl dimethylcarbamate		C₁₄H₁₈N₂O₅	详情	详情
(IV)	24699	3-(2-bromoacetyl)-5-[[(dimethylamino)carbonyl]oxy]phenyl dimethylcarbamate		C₁₄H₁₇BrN₂O₅	详情	详情
(V)	24700	N-benzyl-2-methyl-2-propanamine	3378-72-1	C₁₁H₁₇N	详情	详情
(VI)	24701	3-[2-[benzyl(tert-butyl)amino]acetyl]-5-[[(dimethylamino)carbonyl]oxy]phenyl dimethylcarbamate		C₂₅H₃₃N₃O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：

1) The condensation of 4-(3-hydroxypropyl)-1H-imidazole (I) with dimethylcarbamoyl chloride by means of triethylamine in refluxing acetonitrile followed by reaction with trimethylchlorosilane gives 1-(dimethylcarbamoyl)-4-[3-(trimethylsilyloxy)propyl]imidazole (II), which is condensed with 4-cyanobenzyl bromide (III) in refluxing acetonitrile yielding 1-(4-cyanobenzyl)-5-(3-hydroxypropyl)imidazole (IV). The reaction of (IV) with SOCl2 in refluxing dichloromethane affords the corresponding 3-chloropropyl derivative (V), which is finally cyclized by means of potassium tert-butoxide in THF.

参考文献中间体

合成目标

【1】 Browne, L.J. (Ciba Geigy Corp.); Substituted imidazo[1,5-A]pyridine derivatives as aromatase inhibitors.. ES 8801262; JP 61012688; US 4617307 .
【2】 Pento, J.T.; Prous, J.; Castaner, J.; CGS-16949A. Drugs Fut 1989, 14, 9, 843.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13708	N,N'-Dimethylcarbamoyl chloride; Dimethylcarbamoyl chloride; [(Chlorocarbonyl)(methyl)amino]methane	79-44-7	C₃H₆ClNO	详情	详情
(I)	21245	3-(1H-imidazol-4-yl)-1-propanol		C₆H₁₀N₂O	详情	详情
(II)	21246	N,N-dimethyl-4-[4-(trimethylsilyl)butyl]-1H-imidazole-1-carboxamide		C₁₃H₂₅N₃OSi	详情	详情
(III)	14200	4-(Bromomethyl)benzonitrile; alpha-Bromo-p-tolunitrile	17201-43-3	C₈H₆BrN	详情	详情
(IV)	21248	4-[[5-(3-hydroxypropyl)-1H-imidazol-1-yl]methyl]benzonitrile		C₁₄H₁₅N₃O	详情	详情
(V)	21249	4-[[5-(3-chloropropyl)-1H-imidazol-1-yl]methyl]benzonitrile		C₁₄H₁₄ClN₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

The cyclization of m-anisidine (I) with 2,4-dimethoxyphenylmalonic acid diethyl ester (II) in refluxing diphenyl ether (270-90 C) gives 3-(2,4-dimethoxyphenyl)-4-hydroxy-7-methoxyquinolin-2-(1H)-one (III), which is submitted to a new cyclization process in refluxing 47% aqueous HBr yielding 3,9-dihydroxybenzofuro[3,2-c]quinolin-6-(5H)-one (IV). Finally, this compound is esterified with N,N-dimethylcarbamoyl chloride (V) by means of triethylamine and dimethylaminopyridine (DMAP) in DMF.

参考文献中间体

合成目标

【1】 Rabasseda, X.; Castaner, J.; Mealy, N.; KCA-098. Drugs Fut 1995, 20, 3, 235.
【2】 Kamijo, T.; Ujiie, A.; Harada, H.; Tsutsumi, N.; Tsubaki, A.; Yamaguchi, T.; Nagata, H. (Kissei Pharmaceutical Co., Ltd.); Benzofuro[3,2-c]quinoline cpds. AU 8930977; EP 0357172; JP 1990062878; US 5023261 .

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)	13704	3-Methoxyphenylamine; 3-Methoxyaniline; m-Anisidine	536-90-3	C₇H₉NO	详情	详情
(II)	13705	diethyl 2-(2,4-dimethoxyphenyl)malonate		C₁₅H₂₀O₆	详情	详情
(III)	13706	3-(2,4-Dimethoxyphenyl)-4-hydroxy-7-methoxy-2(1H)-quinolinone		C₁₈H₁₇NO₅	详情	详情
(IV)	13707	3,9-Dihydroxy[1]benzofuro[3,2-c]quinolin-6(5H)-one		C₁₅H₉NO₄	详情	详情
(V)	13708	N,N'-Dimethylcarbamoyl chloride; Dimethylcarbamoyl chloride; [(Chlorocarbonyl)(methyl)amino]methane	79-44-7	C₃H₆ClNO	详情	详情

Extended Information