1-chloro-1-[(chlorocarbonyl)oxy]ethane -Drug Synthesis Database

【结构式】

【分子编号】22014

【品名】1-chloro-1-[(chlorocarbonyl)oxy]ethane

【CA登记号】50893-53-3

【分子式】C₃H₄Cl₂O₂

【分子量】142.96896

【元素组成】C 25.2% H 2.82% Cl 49.59% O 22.38%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

The reaction of 1-chloroethyl chloroformate (I) with cyclohexanol (II) by means of pyridine in dichloromethane gives 1-chloroethyl cyclohexyl carbonate (III), which is converted to the corresponding iodoethyl derivative (IV) with NaI in hot acetonitrile. Finaly this compound is condensed with potassium 7beta-[2-(2-aminothiazol-4-yl)acetamido]-3-[1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylate (V) in DMF.

参考文献中间体

合成目标

【1】 Yashiki, T.; Nishimura, T.; Numata, M.; Hirai, S.; Takanohashi, K.; Miyake, A.; Yoshimura, Y.; Hamaguchi, N.; Yamaoka, M.; Orally active 1-(cyclohexyloxycarbonyloxy)alkyl es. J Antibiot 1987, 40, 1, 81.
【2】 Hirai, S.; Koyama, H.; Makino, T. (Takeda Chemical Industries, Ltd.); Antibacterial solid compsn. for oral administratio. EP 0163433; JP 1985233012; JP 1987030713 .
【3】 Castaner, J.; Prous, J.; SCE-2174. Drugs Fut 1988, 13, 3, 231.

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)	22014	1-chloro-1-[(chlorocarbonyl)oxy]ethane	50893-53-3	C₃H₄Cl₂O₂	详情	详情
(II)	11306	Cyclohexanol	108-93-0	C₆H₁₂O	详情	详情
(III)	15573	1-chloroethyl cyclohexyl carbonate		C₉H₁₅ClO₃	详情	详情
(IV)	15339	cyclohexyl 1-iodoethyl carbonate	102672-57-1	C₉H₁₅IO₃	详情	详情
(V)	22018	potassium (7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-3-[([1-[2-(dimethylamino)ethyl]-1H-1,2,3,4-tetraazol-5-yl]sulfanyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate		C₁₈H₂₂KN₉O₄S₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：

Condensation of acid chloride (VIII) 3-aminotropane (IX) provided amide (X). N-Demethylation of (X) was then achieved by treatment with 1-chloroethyl chloroformate, followed by hydrolysis and decarboxylation of the intermediate carbamate (XI) with MeOH. The resulting secondary amine (XII) was then alkylated with 3-bromopropanol (XIII) to afford the target hydroxypropyl derivative.

参考文献中间体

合成目标

【1】 Yokomori, S.; Muramatsu, M.; Suzuki, M.; Ito, C.; Asanuma, H.; Isobe, Y.; Ohuchi, Y.; Kaneko, T.; Synthesis and evaluation of novel 2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives as potent and selective serotonin 5-HT4 receptor agonists. Chem Pharm Bull 2001, 49, 1, 29.
【2】 Ohuchi, Y.; Suzuki, M.; Asanuma, H.; Yokomori, S.; Hatayama, K. (Taisho Pharmaceutical Co., Ltd.); Quinolinecarboxylic acid deriv.. EP 0710662; JP 1996034784; US 5753673; WO 9531455 .

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
(VIII)	36336	1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarbonyl chloride		C₁₃H₁₂ClNO₂	详情	详情
(IX)	12412	(1R,5S)-8-Methyl-8-azabicyclo[3.2.1]octan-3-amine; (1R,5S)-8-Methyl-8-azabicyclo[3.2.1]oct-3-ylamine		C₈H₁₆N₂	详情	详情
(X)	36337	1-isopropyl-N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-2-oxo-1,2-dihydro-3-quinolinecarboxamide		C₂₁H₂₇N₃O₂	详情	详情
(XI)	36338	1-chloroethyl (1R,5S)-3-[[(1-isopropyl-2-oxo-1,2-dihydro-3-quinolinyl)carbonyl]amino]-8-azabicyclo[3.2.1]octane-8-carboxylate		C₂₃H₂₈ClN₃O₄	详情	详情
(XII)	36339	N-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl]-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide		C₂₀H₂₅N₃O₂	详情	详情
(XIII)	12573	3-Bromo-1-propanol; 3-Bromopropanol	627-18-9	C₃H₇BrO	详情	详情

合成路线3

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

合成路线4

该中间体在本合成路线中的序号：(II)

Treatment of p-nitrophenol (I) with 1-chloroethyl chloroformate (II) in the presence of pyridine afforded carbonate (III). Subsequent displacement of the chlorine atom of (III) with mercuric acetate in HOAc provided the acetoxy derivative (IV). This was then condensed with (R)-alpha-methylhistamine (V) in HMPT to furnish the title compound.

参考文献中间体

合成目标

【1】 Stark, H.; et al.; Enzyme-catalyzed prodrug approaches for the histamine H3-receptor agonist (R)-alpha-methylhistamine. Bioorg Med Chem 2001, 9, 1, 191.

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)	11236	4-Nitrophenol; p-Nitrophenol	100-02-7	C₆H₅NO₃	详情	详情
(II)	22014	1-chloro-1-[(chlorocarbonyl)oxy]ethane	50893-53-3	C₃H₄Cl₂O₂	详情	详情
(III)	51393	1-chloroethyl 4-nitrophenyl carbonate		C₉H₈ClNO₅	详情	详情
(IV)	50378	1-[[(4-nitrophenoxy)carbonyl]oxy]ethyl acetate		C₁₁H₁₁NO₇	详情	详情
(V)	51394	(2R)-1-(1H-imidazol-4-yl)-2-propanamine; (1R)-2-(1H-imidazol-4-yl)-1-methylethylamine		C₆H₁₁N₃	详情	详情

Extended Information