benzoyl isocyanate -Drug Synthesis Database

【结构式】

【分子编号】40601

【品名】benzoyl isocyanate

【CA登记号】4461-33-0

【分子式】C₈H₅NO₂

【分子量】147.13324

【元素组成】C 65.31% H 3.43% N 9.52% O 21.75%

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：

Condensation of 4-amino-1-benzylpiperidine (I) with benzoyl isocyanate gave the benzoyl urea (II), which was subsequently hydrolyzed to urea (III) with NaOH in aqueous methanol. Then, condensation of (III) with 2-hydroxypropiophenone (IV) in the presence of trifluoroacetic acid afforded a mixture of minor amounts of the required imidazolone (V) along with the major undesired regioisomer (VI).

参考文献中间体

合成目标

【1】 Carling, R.W.; Moyes, C.R.; Moore, K.W.; et al.; 1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: A selective high-affinity antagonist for the human dopamine D(4) receptor with excellent selectivity over ion channels. J Med Chem 1999, 42, 14, 2706.
【2】 Carling, W.R.; Moore, K.W. (Merck Sharp & Dohme Ltd.); Imidazolone and oxazolone derivs. as dopamine antagonists. EP 0719264; JP 1997504272; US 5698573; WO 9507904 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40601	benzoyl isocyanate	4461-33-0	C₈H₅NO₂	详情	详情
(I)	34808	1-Benzyl-4-piperidinylamine; 1-Benzyl-4-piperidinamine; 4-Amino-1-benzylpiperidine	50541-93-0	C₁₂H₁₈N₂	详情	详情
(II)	34809	N-benzoyl-N'-(1-benzyl-4-piperidinyl)urea		C₂₀H₂₃N₃O₂	详情	详情
(III)	34810	N-(1-benzyl-4-piperidinyl)urea		C₁₃H₁₉N₃O	详情	详情
(IV)	34811	2-hydroxy-1-phenyl-1-propanone		C₉H₁₀O₂	详情	详情
(V)	34812	1-(1-benzyl-4-piperidinyl)-5-methyl-4-phenyl-1,3-dihydro-2H-imidazol-2-one		C₂₂H₂₅N₃O	详情	详情
(VI)	34813	1-(1-benzyl-4-piperidinyl)-4-methyl-5-phenyl-1,3-dihydro-2H-imidazol-2-one		C₂₂H₂₅N₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：

Aminopiperidine (I) was alkylated with 2-bromopropiophenone (VII), and the resulting unstable aminoketone (VIII) was treated with benzoyl isocyanate to produce the benzoyl urea (IX). Cyclization of (IX), followed by benzoyl group cleavage upon treatment with methanolic NaOMe gave the hydroxy imidazolinone (X). This was dehydrated to the imidazolone (V) by means of trifluoroacetic acid. The intermediate (V) was debenzylated to (XII) by reaction with 1-chloroethyl chloroformate, followed by treatment of the resulting (1-chloroethyl) carbamate (XI) with boiling MeOH. The debenzylated piperidine (XII) was finally alkylated with alpha-bromo-m-tolunitrile (XIII) to give the target m-cyanobenzyl derivative.

参考文献中间体

合成目标

【1】 Carling, R.W.; Moyes, C.R.; Moore, K.W.; et al.; 1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: A selective high-affinity antagonist for the human dopamine D(4) receptor with excellent selectivity over ion channels. J Med Chem 1999, 42, 14, 2706.
【2】 Carling, W.R.; Moore, K.W. (Merck Sharp & Dohme Ltd.); Imidazolone and oxazolone derivs. as dopamine antagonists. EP 0719264; JP 1997504272; US 5698573; WO 9507904 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	22014	1-chloro-1-[(chlorocarbonyl)oxy]ethane	50893-53-3	C₃H₄Cl₂O₂	详情	详情
	40601	benzoyl isocyanate	4461-33-0	C₈H₅NO₂	详情	详情
(I)	34808	1-Benzyl-4-piperidinylamine; 1-Benzyl-4-piperidinamine; 4-Amino-1-benzylpiperidine	50541-93-0	C₁₂H₁₈N₂	详情	详情
(V)	34812	1-(1-benzyl-4-piperidinyl)-5-methyl-4-phenyl-1,3-dihydro-2H-imidazol-2-one		C₂₂H₂₅N₃O	详情	详情
(VII)	34814	2-bromo-1-phenyl-1-propanone	2114-00-3	C₉H₉BrO	详情	详情
(VIII)	34815	2-[(1-benzyl-4-piperidinyl)amino]-1-phenyl-1-propanone		C₂₁H₂₆N₂O	详情	详情
(IX)	34816	N'-benzoyl-N-(1-benzyl-4-piperidinyl)-N-(1-methyl-2-oxo-2-phenylethyl)urea		C₂₉H₃₁N₃O₃	详情	详情
(X)	34817	1-(1-benzyl-4-piperidinyl)-4-hydroxy-5-methyl-4-phenyl-2-imidazolidinone		C₂₂H₂₇N₃O₂	详情	详情
(XI)	34818	1-chloroethyl 4-(5-methyl-2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)-1-piperidinecarboxylate		C₁₈H₂₂ClN₃O₃	详情	详情
(XII)	34819	5-methyl-4-phenyl-1-(4-piperidinyl)-1,3-dihydro-2H-imidazol-2-one		C₁₅H₁₉N₃O	详情	详情
(XIII)	13244	alpha-Bromo-m-tolunitrile; 3-(Bromomethyl)benzonitrile	28188-41-2	C₈H₆BrN	详情	详情

Extended Information