Pentanenitrile; n-Valeronitrile -Drug Synthesis Database

【结构式】

【分子编号】13921

【品名】Pentanenitrile; n-Valeronitrile

【CA登记号】110-59-8

【分子式】C₅H₉N

【分子量】83.1332

【元素组成】C 72.24% H 10.91% N 16.85%

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：(I)

Synthesis of imidazole (V) first entails the conversion of valeronitrile (I) to its imidate ester (II). Subsequent reaction with 1,3-dihydroxyacetone dimer and ammonia leads to imidazole (III). Chlorination with N-chlorosuccinimide yields the 4-chloroimidazole (IV). Oxidation with manganese dioxide finally yields imidazole-5-carboxaldehyde (V).

参考文献中间体

合成目标

【1】 Carini, D.J.; Duncia, J.V.; Aldrich, P.E.; Chiu, A.T.; Johnson, A.L.; Pierce, M.E.; Santella, J.B.; Wells, G.J.; Wexler, R.R.; Wong, P.C.; Timmermans, P.B.M.W.M.; Nonpeptide angiotensin II receptor antagonists: The discovery of a series of N-(biphenylmethyl)imidazoles as potent, orally-active antihypertensives. J Med Chem 1991, 34, 8, 2225-47.
【2】 Duncia, J.V.; Carini, D.J.; Chiu, A.T.; Pierce, M.E.; Price, W.A.; Smith, R.D.; Wells, G.J.; Wong, P.C.; Wexler, R.R.; Johnson, A.L.; Timmermans, P.B.M.W.M.; DuP 753. Drugs Fut 1991, 16, 4, 305.

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)	13921	Pentanenitrile; n-Valeronitrile	110-59-8	C₅H₉N	详情	详情
(II)	13922	Methyl pentanimidoate hydrocloride		C₆H₁₄ClNO	详情	详情
(III)	13923	2-Butyl-5-hydroxymethylimidazole; (2-Butyl-1H-imidazol-5-yl)methanol	68283-19-2	C₈H₁₄N₂O	详情	详情
(IV)	13924	2-Butyl-4-chloro-5-(hydroxymethyl)imidazole; (2-Butyl-4-chloro-1H-imidazol-5-yl)methanol	79047-41-9	C₈H₁₃ClN₂O	详情	详情
(V)	13925	2-Butyl-4-chloro-1H-imidazole-5-carbaldehyde	83857-96-9	C₈H₁₁ClN₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

Several novel syntheses of 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde (XI), a key intermediate in the synthesis of losartan, have been described: 1) Treatment of glycine methyl ester hydrochloride (I) with NaOH in methanol, followed by reaction with methyl pentanimidate (II), gives 2-butyl-4,5-dihydro-1H-imidazol-5-one (III), which is treated with POCl3 to give the 2-butyl-5-chloro-1H-imidazole (IV). Reaction of (IV) with POCl3 and DMF yields the enamine (V), which is finally hydrolyzed with water to 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde (XI), the desired intemediate in the synthesis of losartan. 2) Imidazolinone (III) can also be obtained by cyclization of chloroacetic acid methyl ester (VI), chloroacetyl chloride (VII) or bromoacetyl bromide (VIII) with pentanamidine (IX) by means of NaOH in methanol. 3) Alternatively, imidazolinone (III) can be treated with dimethylformamide dimethylacetal in dichloromethane yielding the enamine (X), which is finally treated with POCl3 and hydrolyzed with water. 4) The reaction of glycine (XI) with methyl pentanimidate (II) in NaOH/MeOH gives amidine (XII), which, without isolation, is treated with POCl3 and DMF at 100 C for 2 h, and then hydrolyzed with water to give the desired 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde. Methyl pentanimidate (II) is obtained treating a solution of valeronitrile in MeOH with HCl gas followed by neutralization with aqueous KOH and extraction with Et2O.

参考文献中间体

合成目标

【1】 Kohr, J.; Griffiths, G.J.; Imwinkelried, R.; Hauck, M.B.; Roten, C.A.; Stucky, G.C.; Novel syntheses of 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde: A key intermediate for the synthesis of the angiotensin II antagonist losartan. J Org Chem 1999, 64, 22, 8084.

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)	17568	methyl 2-aminoacetate		C₃H₇NO₂	详情	详情
(II)	34050	methyl pentanimidoate		C₆H₁₃NO	详情	详情
(III)	34051	2-butyl-3,5-dihydro-4H-imidazol-4-one		C₇H₁₂N₂O	详情	详情
(IV)	34052	2-butyl-5-chloro-1H-imidazole		C₇H₁₁ClN₂	详情	详情
(V)	34053	N-[(2-butyl-5-chloro-4H-imidazol-4-ylidene)methyl]-N,N-dimethylamine; (2-butyl-5-chloro-4H-imidazol-4-ylidene)-N,N-dimethylmethanamine		C₁₀H₁₆ClN₃	详情	详情
(VI)	10257	methyl 2-chloroacetate; methyl chloroacetate	96-34-4	C₃H₅ClO₂	详情	详情
(VII)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(VIII)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(IX)	14576	pentanimidamide	109-51-3	C₅H₁₂N₂	详情	详情
(X)	34054	2-butyl-5-[(E)-(dimethylamino)methylidene]-3,5-dihydro-4H-imidazol-4-one		C₁₀H₁₇N₃O	详情	详情
(XI)	13925	2-Butyl-4-chloro-1H-imidazole-5-carbaldehyde	83857-96-9	C₈H₁₁ClN₂O	详情	详情
(XII)	20436	glycine	56-40-6	C₂H₅NO₂	详情	详情
(XIII)	34055	2-(pentanimidoylamino)acetic acid		C₇H₁₄N₂O₂	详情	详情
(XIV)	13921	Pentanenitrile; n-Valeronitrile	110-59-8	C₅H₉N	详情	详情

Extended Information