N-(cyclopropylmethyl)-1-propanamine -Drug Synthesis Database

【结构式】

【分子编号】27745

【品名】N-(cyclopropylmethyl)-1-propanamine

【CA登记号】26389-60-6

【分子式】C₇H₁₅N

【分子量】113.20284

【元素组成】C 74.27% H 13.36% N 12.37%

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：(IV)

The condensation of 4,6-dichloro-2-methylpyrimidine (I) with 2,4,6-trichloroaniline (II) by means of NaH in THF gives N-(6-chloro-2-methylpyrimidin-4-yl)-N-(2,4,6-trichlorophenyl)amine (III), which is condensed with N-(cyclopropylmethyl)-N-propylamine (IV) by heating at 100-190 C yielding N-(cyclopropylmethyl)-N-[2-methyl-6-(2,4,6-trichlorophenylamino)-pyrimidin-4-yl]-N-propylamine (V). Finally, this compound is chlorinated with N-chlorosuccinimide (NCS) in refluxing chloroform.

参考文献中间体

合成目标

【1】 Dagnino, R. jr.; Chen, C.; de Souzza, E.B.; et al.; Design and synthesis of a series of non-peptide high-affinity human corticotropin-releasing factor1 receptor antagonists. J Med Chem 1996, 39, 22, 4360.

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)	32323	4,6-dichloro-2-methylpyrimidine	1780-26-3	C₅H₄Cl₂N₂	详情	详情
(II)	15466	2,4,6-Trichloroaniline; 2,4,6-Trichlorophenylamine	634-93-5	C₆H₄Cl₃N	详情	详情
(III)	32324	N-(6-chloro-2-methyl-4-pyrimidinyl)-N-(2,4,6-trichlorophenyl)amine; 6-chloro-2-methyl-N-(2,4,6-trichlorophenyl)-4-pyrimidinamine		C₁₁H₇Cl₄N₃	详情	详情
(IV)	27745	N-(cyclopropylmethyl)-1-propanamine	26389-60-6	C₇H₁₅N	详情	详情
(V)	32325	N-(cyclopropylmethyl)-N-[2-methyl-6-(2,4,6-trichloroanilino)-4-pyrimidinyl]-N-propylamine; N(4)-(cyclopropylmethyl)-2-methyl-N(4)-propyl-N(6)-(2,4,6-trichlorophenyl)-4,6-pyrimidinediamine		C₁₈H₂₁Cl₃N₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Suzuki coupling of 2-bromoaniline (I) with boronic acid (II) in the presence of a palladium catalyst gave biphenyl (III). Subsequent condensation of (III) with ethyl acetoacetate (IV) afforded enamine (V), which was cyclized to hydroxyquinoline (VI) in refluxing diphenyl ether. Chlorination of (VI) in boiling POCl3 produced the corresponding 4-chloroquinoline (VII). This was finally condensed with N-(cyclopropylmethyl)-N--propylamine (VIII) to provide the target aminoquinoline.

参考文献中间体

合成目标

【1】 Huang, C.; Chen, C.; McCarthy, J.R.; Haddach, M.; Wilcoxen, K.M. (Janssen Pharmaceutica NV; Neurocrine Biosciences Inc.); CRF antagonistic quino- and quinazolines. EP 0977737; WO 9847874 .

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)	27739	2-bromoaniline	615-36-1	C₆H₆BrN	详情	详情
(II)	27740	mesitylboronic acid	5980-97-2	C₉H₁₃BO₂	详情	详情
(III)	27741	2',4',6'-trimethyl[1,1'-biphenyl]-2-amine		C₁₅H₁₇N	详情	详情
(IV)	11819	ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate	141-97-9	C₆H₁₀O₃	详情	详情
(V)	27742	ethyl (E)-3-(2-mesitylanilino)-2-butenoate		C₂₁H₂₅NO₂	详情	详情
(VI)	27743	8-mesityl-2-methyl-4-quinolinol		C₁₉H₁₉NO	详情	详情
(VII)	27744	4-chloro-8-mesityl-2-methylquinoline		C₁₉H₁₈ClN	详情	详情
(VIII)	27745	N-(cyclopropylmethyl)-1-propanamine	26389-60-6	C₇H₁₅N	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Condensation between 4,6-dichloro-2-methylpyrimidine (I) and 2,6-dichloro-4-iodoaniline (II) in the presence of NaH in THF furnished the diaryl amine (III). The remaining chlorine atom was displaced with N-(cyclopropylmethyl)propylamine (IV) in hot DMSO to yield (V). Finally, chlorination of the pyrimidine ring with N-chlorosuccinimide (NCS) afforded the target 4-iodo derivative.

参考文献中间体

合成目标

【1】 Hsin, L.-W.; Webster, E.L.; Tian, X.; et al.; The development of a potential single photon emission computed tomography (SPECT) imaging agent for the corticotropin-releasing hormone receptor type 1. Bioorg Med Chem Lett 2001, 11, 3, 331.

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)	32323	4,6-dichloro-2-methylpyrimidine	1780-26-3	C₅H₄Cl₂N₂	详情	详情
(II)	51390	2,6-dichloro-4-iodophenylamine; 2,6-dichloro-4-iodoaniline		C₆H₄Cl₂IN	详情	详情
(III)	51391	N-(6-chloro-2-methyl-4-pyrimidinyl)-N-(2,6-dichloro-4-iodophenyl)amine; 6-chloro-N-(2,6-dichloro-4-iodophenyl)-2-methyl-4-pyrimidinamine		C₁₁H₇Cl₃IN₃	详情	详情
(IV)	27745	N-(cyclopropylmethyl)-1-propanamine	26389-60-6	C₇H₁₅N	详情	详情
(V)	51392	N-(cyclopropylmethyl)-N-[6-(2,6-dichloro-4-iodoanilino)-2-methyl-4-pyrimidinyl]-N-propylamine; N(4)-(cyclopropylmethyl)-N(6)-(2,6-dichloro-4-iodophenyl)-2-methyl-N(4)-propyl-4,6-pyrimidinediamine		C₁₈H₂₁Cl₂IN₄	详情	详情

Extended Information