o-Chlorobenzoyl chloride; 2-Chlorobenzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】14000

【品名】o-Chlorobenzoyl chloride; 2-Chlorobenzoyl chloride

【CA登记号】609-65-4

【分子式】C₇H₄Cl₂O

【分子量】175.01356

【元素组成】C 48.04% H 2.3% Cl 40.51% O 9.14%

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)

The condensation of 2-chlorobenzoyl chloride (I) with cyanacetic acid (II) by means of butyllithium in THF gives 2-(2-chlorobenzoyl)acetonitrile (III), which is cyclized with N-(ethoxycarbonyl)piperidin-4-one (IV) by means of S and morpholine in refluxing methanol yielding the bicyclic ethyl ester (V). The acylation of (V) with bromoacetyl bromide (VI) in chloroform affords the corresponding 2-(bromoacetamido) derivative (VII), which by reaction with dry ammonia in THF is converted into the 2-glycinamido derivative (VIII). The cyclization of (VIII) in refluxing pyridine gives the tricyclic ethyl ester (IX), which by reaction with P2S5 in refluxing pyridine is converted into the corresponding thioketone (X). The reaction of (X) with hydrazine in methanol yields the 2-hydrazino derivative (XI), which is acylated with acetyl chloride (XII) and NaHCO3 in THF affording the 2-(acetylhydrazino) derivative (XIII). The cyclization of (XIII) in refluxing acetic acid gives the tetracyclic ethyl ester (XIV), which is decarboxylated with 30% HBr yielding the tetracyclic precursor (XV). The acylation of (XV) with 2-(3,4-dimethoxyphenylthio)acetic acid (XVI) by means of dicyclohexylcarbodiimide (DCC) in DMF affords the acylated compound (XVII), which is finally treated with P2S5 or Lawesson's reagent.

参考文献中间体

合成目标

【1】 Braquet, P.; Esanu, A.; Laurent, J.-P.; Pommier, J. (SCRAS (Societé de Conseils de Recherches et d'Applications Scientifiques)); Thieno-triazolo-diazepine derivs. and process for their preparation. BE 1004122; CH 681009; DE 4015137; FR 2646774; FR 2646851; GB 2231330; JP 1991005484; US 5049559 .
【2】 Braquet,P.; Castaner, J.; Duverger, D.; Koltai, M.; Spinnewyn, B.; Pirotzky, E.; Esanu, A.; BN 50739. Drugs Fut 1991, 16, 5, 413.

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)	14000	o-Chlorobenzoyl chloride; 2-Chlorobenzoyl chloride	609-65-4	C₇H₄Cl₂O	详情	详情
(II)	12591	Cyanoacetic Acid; 2-Cyanoacetic acid	372-09-8	C₃H₃NO₂	详情	详情
(III)	12923	3-(2-Chlorophenyl)-3-oxopropanenitrile	40018-25-5	C₉H₆ClNO	详情	详情
(IV)	13486	Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone	29976-53-2	C₈H₁₃NO₃	详情	详情
(V)	14004	ethyl 2-amino-3-(2-chlorobenzoyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate		C₁₇H₁₇ClN₂O₃S	详情	详情
(VI)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(VII)	14006	ethyl 2-[(2-bromoacetyl)amino]-3-(2-chlorobenzoyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate		C₁₉H₁₈BrClN₂O₄S	详情	详情
(VIII)	14007	ethyl 2-[(2-aminoacetyl)amino]-3-(2-chlorobenzoyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate		C₁₉H₂₀ClN₃O₄S	详情	详情
(IX)	14008	ethyl 5-(2-chlorophenyl)-2-oxo-1,2,3,6,7,9-hexahydro-8H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepine-8-carboxylate		C₁₉H₁₈ClN₃O₃S	详情	详情
(X)	14009	ethyl 5-(2-chlorophenyl)-2-thioxo-1,2,3,6,7,9-hexahydro-8H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepine-8-carboxylate		C₁₉H₁₈ClN₃O₂S₂	详情	详情
(XI)	14010	ethyl 5-(2-chlorophenyl)-2-hydrazino-3,6,7,9-tetrahydro-8H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepine-8-carboxylate		C₁₉H₂₀ClN₅O₂S	详情	详情
(XII)	14011	1-(Chlorooxy)-1-oxoethane		C₂H₃ClO₂	详情	详情
(XIII)	14012	ethyl 2-(2-acetylhydrazino)-5-(2-chlorophenyl)-3,6,7,9-tetrahydro-8H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepine-8-carboxylate		C₂₁H₂₂ClN₅O₃S	详情	详情
(XIV)	14013	ethyl 6-(2-chlorophenyl)-1-methyl-7,10-dihydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-9(8H)-carboxylate		C₂₁H₂₀ClN₅O₂S	详情	详情
(XV)	14014	6-(2-Chlorophenyl)-1-methyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine		C₁₈H₁₆ClN₅S	详情	详情
(XVI)	14015	2-[(3,4-Dimethoxyphenyl)sulfanyl]acetic acid	95735-63-0	C₁₀H₁₂O₄S	详情	详情
(XVII)	14016	1-[6-(2-Chlorophenyl)-1-methyl-7,10-dihydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-9(8H)-yl]-2-[(3,4-dimethoxyphenyl)sulfanyl]-1-ethanone		C₂₈H₂₆ClN₅O₃S₂	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 acetophenone (I) with 2-chlorobenzoyl chloride (II) in pyridine gives the corresponding ester (III), which is treated with KOH in hot pyridine yielding the diketone (IV). The cyclization of (IV) with H2SO4 in acetic acid at 100 C affords the benzopyranone (V). The hydrolysis of the acetate group of (V) with NaOH in methanol/water affords the piperidinol (VI), which is finally demethylated with pyridinium hydrochloride at 210-20 C. Alternatively, the ester (III) can be cyclized directly to benzopyranone (V) by means of NaH in hot dioxane.

参考文献中间体

合成目标

【1】 Naik, R.G.; Lal, B.; Rupp, R.H.; Sedlacek, H.H.; Dickneite, G.; Czech, J. (Aventis SA); Use of 4H-1-benzopyran-4-one derivs., 4H-1-benzopyran-4-one derivs. and medicines containing same. AU 8943841; DE 3836676; EP 0366061; JP 1990178225; US 5284856 .
【2】 Tabaka, A.C.; et al.; Application of modified flavone closure for the preparation of racemic L86-8275. Org Process Res Dev 1999, 3, 4, 256.

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)	38042	(3R,4R)-4-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methylpiperidinyl acetate		C₁₈H₂₅NO₆	详情	详情
(II)	14000	o-Chlorobenzoyl chloride; 2-Chlorobenzoyl chloride	609-65-4	C₇H₄Cl₂O	详情	详情
(III)	38043	2-acetyl-6-[(3R,4R)-3-(acetoxy)-1-methylpiperidinyl]-3,5-dimethoxyphenyl 2-chlorobenzoate		C₂₅H₂₈ClNO₇	详情	详情
(IV)	38044	(3R,4R)-4-[3-[3-(2-chlorophenyl)-3-oxopropanoyl]-2-hydroxy-4,6-dimethoxyphenyl]-1-methylpiperidinyl acetate		C₂₅H₂₈ClNO₇	详情	详情
(V)	38045	(3R,4R)-4-[2-(2-chlorophenyl)-5,7-dimethoxy-4-oxo-4H-chromen-8-yl]-1-methylpiperidinyl acetate		C₂₅H₂₆ClNO₆	详情	详情
(VI)	38046	2-(2-chlorophenyl)-8-[(3R,4R)-3-hydroxy-1-methylpiperidinyl]-5,7-dimethoxy-4H-chromen-4-one		C₂₃H₂₄ClNO₅	详情	详情

Extended Information