3,4-dichlorobenzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】26356

【品名】3,4-dichlorobenzoyl chloride

【CA登记号】3024-72-4

【分子式】C₇H₃Cl₃O

【分子量】209.45832

【元素组成】C 40.14% H 1.44% Cl 50.78% O 7.64%

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 Friedel-Kraft's reaction of benzene (I) and 3,4-dichlorobenzoyl chloride (II) by means of AlCl3 in dichloromethane gives 3,4-dichlorobenzophenone (III), which is condensed with diethyl succinate (IV) by means of potassium tert-butoxide in tert-butyl alcohol yielding ethyl 3-ethoxycarbonyl-4-(3,4-dichlorophenyl)-4-phenylbut-3-enoate (V). Hydrolysis of (V) with HBr in refluxing acetic acid affords 4-(3,4-dichlorophenyl)-4-phenylbut-3-enoic acid (VI), which is hydrogenated with H2 over Pd/C in ethyl acetate giving 4-(3,4-dichlorophenyl)-4-phenylbutanoic acid (VII), which is converted into the corresponding acyl chloride (VIII) with refluxing SOCl2. Cyclization of (VIII) with AlCl3 in CS2 yields 4-(3,4-dichlorophenyl)-3,4-dihydro-1-(2H)-naphthalenone (IX), which is treated with methylamine and TiCl4 in THF affording the corresponding Schiff base (X). Finally, this compound is reduced with H2 over Pd/C in THF.

参考文献中间体

合成目标

【1】 Kraska, A.R.; Welch, W.M. Jr.; Koe, B.K.; Harbert, C.A. (Pfizer Inc.); Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphtalenamine. EP 0030081; JP 1981086137; US 4536518 .
【2】 Castaner, J.; Serradell, M.N.; Sertraline. Drugs Fut 1984, 9, 4, 277.

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)	13364	Benzene	71-43-2	C₆H₆	详情	详情
(II)	26356	3,4-dichlorobenzoyl chloride	3024-72-4	C₇H₃Cl₃O	详情	详情
(III)	30578	(3,4-dichlorophenyl)(phenyl)methanone	6284-79-3	C₁₃H₈Cl₂O	详情	详情
(IV)	12313	diethyl succinate	123-25-1	C₈H₁₄O₄	详情	详情
(V)	30579	diethyl 2-[(Z)-(3,4-dichlorophenyl)(phenyl)methylidene]succinate		C₂₁H₂₀Cl₂O₄	详情	详情
(VI)	30580	(E)-4-(3,4-dichlorophenyl)-4-phenyl-3-butenoic acid		C₁₆H₁₂Cl₂O₂	详情	详情
(VII)	30581	4-(3,4-dichlorophenyl)-4-phenylbutyric acid		C₁₆H₁₄Cl₂O₂	详情	详情
(VIII)	30582	4-(3,4-dichlorophenyl)-4-phenylbutanoyl chloride		C₁₆H₁₃Cl₃O	详情	详情
(IX)	30583	4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone; 4-(3',4'-Dichlorophenyl)-1-tetralone	79580-19-3	C₁₆H₁₂Cl₂O	详情	详情
(X)	30584	N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]-N-methylamine; N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine		C₁₇H₁₅Cl₂N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of glutamic acid (I) with 3,4-dichlorobenzoyl chloride (II) by means of Na2CO3 in water gives N-(3,4-dichlorobenzoyl)glutamic acid (III), which is treated with acetic anhydride in refluxing isopropyl ether to afford N-(3,4-dichlorobenzoyl)glutamic anhydride (IV). Finally, this compound is treated with dipentylamine (V) in water.

参考文献中间体

合成目标

【1】 Zrenner, E.; Laties, A.M.; Eur J Med Chem - Chim Ther 1986, 21, 1, 9-20.
【2】 Chiste, R.; Makovec, F.; Rovati, L.A.; Pacini, M.A.; Bani, M.; Setnikar, I.; New glutaramic acid derivatives with potent competitive and specific cholecystokinin-antagonistic activity. Arzneim-Forsch Drug Res 1985, 35, 7, 1048-1051.
【3】 Rovati, L.C.; Chiste, R.; Bani, M.; Revel, L.; Makovec, F.; Rovati, L.A.; Differentiation of central and peripheral cholecystokinin receptors by new glutaramic acid derivatives with cholecystokinin-antagonistic activity. Arzneim-Forsch Drug Res 1986, 36, 1, 98-102.
【4】 Rovati, L.; Makovec, F.; Senin, P.; Chiste', R. (Rotta Research Laboratorium SpA); Derivatives of glutamic acid and aspartic acid. AU 8544109; BE 0902726; CH 674203; DE 3522506; ES 8604859; FR 2566397; GB 2160869; JP 1986044855; US 4791215 .
【5】 Castaner, J.; Serradell, M.N.; Castaner, R.M.; Lorglumide. Drugs Fut 1987, 12, 9, 851.

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)	28752	DL-2-Amino propane dicarboxylic acid; DL-2-Aminopentanoic acid; glutamic acid; DL-glutamic acid; (+/-)-2-Aminoglutaric acid	617-65-2	C₅H₉NO₄	详情	详情
(II)	26356	3,4-dichlorobenzoyl chloride	3024-72-4	C₇H₃Cl₃O	详情	详情
(III)	28750	N-(3,4-dichlorobenzoyl)glutamic acid		C₁₂H₁₁Cl₂NO₅	详情	详情
(IV)	12129	3,4-Dichloro-N-(2,6-dioxotetrahydro-2H-pyran-3-yl)benzamide		C₁₂H₉Cl₂NO₄	详情	详情
(V)	28751	N-pentyl-1-pentanamine	2050-92-2	C₁₀H₂₃N	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 condensation of the N-(benzyloxycarbonyl)-D-glutamic acid 5-benzyl ester (I) with N-(3-methoxypropyl)-N-pentylamine (II) by means of ethyl chloroformate and triethylamine in THF gives the corresponding amide (III), which is debenzylated by hydrogenation over Pd/C in methanol, yielding compound (IV). Finally, the free amino group of (IV) is acylated with 3,4-dichlorobenzoyl chloride (V) by means of NaOH in water to give dexloxiglumide.

参考文献中间体

合成目标

【1】 Castaner, J.; Revel, L.; Makovec, F.; Dexloxiglumide. Drugs Fut 1999, 24, 7, 725.
【2】 Makovec, F.; Chiste, R.; Peris, W.; Rovati, L. (Rotta Research Laboratorium SpA); Derivs. of (R)-5-pentylamino-5-oxopentanoic acid with anticholecystokinin activity. EP 0344184; JP 1988201156; US 5130474; US 5391574; WO 8805774 .

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)	26353	(2R)-5-(benzyloxy)-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoic acid	5680-86-4	C₂₀H₂₁NO₆	详情	详情
(II)	12130	N-(3-Methoxypropyl)-N-pentylamine; N-(3-Methoxypropyl)-1-pentanamine		C₉H₂₁NO	详情	详情
(III)	26354	benzyl (4R)-4-[[(benzyloxy)carbonyl]amino]-5-[(3-methoxypropyl)(pentyl)amino]-5-oxopentanoate		C₂₉H₄₀N₂O₆	详情	详情
(IV)	26355	benzyl (4R)-4-amino-5-[(3-methoxypropyl)(pentyl)amino]-5-oxopentanoate		C₂₁H₃₄N₂O₄	详情	详情
(V)	26356	3,4-dichlorobenzoyl chloride	3024-72-4	C₇H₃Cl₃O	详情	详情

Extended Information