2-(4-methoxyphenyl)acetyl chloride -Drug Synthesis Database

【结构式】

【分子编号】26758

【品名】2-(4-methoxyphenyl)acetyl chloride

【CA登记号】4693-91-8

【分子式】C₉H₉ClO₂

【分子量】184.62196

【元素组成】C 58.55% H 4.91% Cl 19.2% O 17.33%

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：(II)

The condensation of 2,2-dimethyl-7-nitro-2H-1-benzopyran-6-amine (I) with 4-methoxyphenylacetyl chloride (II) by means of triethylmaine in chloroform gives the corresponding amide (III), which is regioselectively epoxidized with ClONa and a chiral manganese catalyst yielding the epoxide (IV). Finally, this compound is treated with cyclopropylamine in refluxing ethanol.

参考文献中间体

合成目标

【1】 Ohrai, K.; Sato, M.; Yanagihara, K.; Tanikawa, K.; Yamashita, T.; Shigeta, Y.; Structure-activity relationships and pharmacological activities of benzopyran derivatives with selective bradycardic and anti-fibrillatory effects. Symp Med Chem 1998, Abst 1-P-29.
【2】 Tanikawa, K.; Ohrai, K.; Sato, M.; Yamashita, T.; Yanagihara, K. (Nissan Chemical Industry, Ltd.); Chroman derivs.. EP 0934296; JP 1998087650; US 6066631; WO 9804542 .

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)	26757	2,2-dimethyl-7-nitro-2H-chromen-6-amine		C₁₁H₁₂N₂O₃	详情	详情
(II)	26758	2-(4-methoxyphenyl)acetyl chloride	4693-91-8	C₉H₉ClO₂	详情	详情
(III)	26759	N-(2,2-dimethyl-7-nitro-2H-chromen-6-yl)-2-(4-methoxyphenyl)acetamide		C₂₀H₂₀N₂O₅	详情	详情
(IV)	26760	N-[(1aR,7bR)-2,2-dimethyl-5-nitro-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl]-2-(4-methoxyphenyl)acetamide		C₂₀H₂₀N₂O₆	详情	详情
(V)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	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 acylation of 6-amino-2,2-dimethyl-7-nitro-2H-1-benzopyran (I) with p-methoxyphenylacetyl chloride (II) furnished amide (III). Subsequent bromination of the pyran ring of (III) employing N-bromosuccinimide in H2O-DMSO formed the trans bromohydrin (IV), which was further cyclized to epoxide (V) upon treatment with NaOH. Finally, oxirane ring opening in (IV) with cyclopropylamine (VI) in boiling EtOH yielded the title trans amino alcohol.

参考文献中间体

合成目标

【1】 Tanikawa, K.; Ohrai, K.; Sato, M.; Yamashita, T.; Yanagihara, K. (Nissan Chemical Industry, Ltd.); Chroman derivs.. EP 0934296; JP 1998087650; US 6066631; WO 9804542 .

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)	26757	2,2-dimethyl-7-nitro-2H-chromen-6-amine		C₁₁H₁₂N₂O₃	详情	详情
(II)	26758	2-(4-methoxyphenyl)acetyl chloride	4693-91-8	C₉H₉ClO₂	详情	详情
(III)	26759	N-(2,2-dimethyl-7-nitro-2H-chromen-6-yl)-2-(4-methoxyphenyl)acetamide		C₂₀H₂₀N₂O₅	详情	详情
(IV)	59601	N-[(3S,4R)-3-bromo-4-hydroxy-2,2-dimethyl-7-nitro-3,4-dihydro-2H-chromen-6-yl]-2-(4-methoxyphenyl)acetamide		C₂₀H₂₁BrN₂O₆	详情	详情
(V)	26760	N-[(1aR,7bR)-2,2-dimethyl-5-nitro-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl]-2-(4-methoxyphenyl)acetamide		C₂₀H₂₀N₂O₆	详情	详情
(VI)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Acylation of 3,5-dimethoxyaniline (I) with 4-methoxyphenylacetyl chloride (II) afforded amide (III). Treatment of (III) with Vilsmeier reagent gave rise to 2-chloroquinoline derivative (IV), which was hydrolyzed to quinolinone (V) using aqueous HOAc. Conjugate addition to (V) of acrylonitrile (VI) produced the cyanoethyl quinolinone (VII). The title tetrazole was then obtained by reaction of nitrile (VII) with tributyltin azide in hot toluene.

参考文献中间体

合成目标

【1】 Guillaumet, G.; Darro, F.; Frydman, A.; Joseph, B.; Kiss, R. (Laboratoires L. Lafon); Pharmaceutical compsns. comprising 2-quinolones. EP 1097138; FR 2781218; WO 0003990 .

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)	25780	3,5-dimethoxyaniline; 3,5-dimethoxyphenylamine	10272-07-8	C₈H₁₁NO₂	详情	详情
(II)	26758	2-(4-methoxyphenyl)acetyl chloride	4693-91-8	C₉H₉ClO₂	详情	详情
(III)	46380	N-(3,5-dimethoxyphenyl)-2-(4-methoxyphenyl)acetamide		C₁₇H₁₉NO₄	详情	详情
(IV)	46381	2-chloro-5,7-dimethoxy-3-(4-methoxyphenyl)quinoline; 4-(2-chloro-5,7-dimethoxy-3-quinolinyl)phenyl methyl ether		C₁₈H₁₆ClNO₃	详情	详情
(V)	46382	5,7-dimethoxy-3-(4-methoxyphenyl)-2(1H)-quinolinone		C₁₈H₁₇NO₄	详情	详情
(VI)	10847	Acrylonitrile	107-13-1	C₃H₃N	详情	详情
(VII)	46383	3-[5,7-dimethoxy-3-(4-methoxyphenyl)-2-oxo-1(2H)-quinolinyl]propanenitrile		C₂₁H₂₀N₂O₄	详情	详情

合成路线4

该中间体在本合成路线中的序号：(XX)

10-Deacetylbaccatin III (XIV) was protected by treatment with triethylsilyl chloride and imidazole, and the resulting trisilylated compound (XV) was debenzoylated to diol (XVI) by using Red-Al(R). Selective coupling of (XVI) with m-anisic acid (XVII) yielded the m-methoxybenzoate ester (XVIII). Complete desilylation of (XVIII) with HF-pyridine, followed by selective resilylation at C-7, furnished (XIX). The 10-hydroxyl group was then selectively acylated with p-methoxyphenylacetyl chloride (XX) to afford ester (XXI). Finally, coupling of the modified baccatin (XXI) with the intermediate lactam (XIII) in the presence of lithium hexamethyldisilazide, and then deprotection with HF-pyridine, gave rise to the desired taxoid.

参考文献中间体

合成目标

【1】 Strum, M.; Tynebor, R.; Pera, P.; Bernacki, R.J.; Ojima, I.; Synthesis and SAR of advanced second generation taxoids. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 132.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	19157	tert-butyl (2S,3R)-2-(2-methyl-1-propenyl)-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate		C₂₁H₃₉NO₄Si	详情	详情
(XIV)	10467	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,9,12,15-tetrahydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate	32981-86-5	C₂₉H₃₆O₁₀	详情	详情
(XV)	51201	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₇H₇₈O₁₀Si₃	详情	详情
(XVI)	51202	(1S,2S,3R,7R,9S,10S,12R,15S)-1,2-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-4-yl acetate		C₄₀H₇₄O₉Si₃	详情	详情
(XVII)	28559	m-Anisic acid; 3-Methoxybenzoic acid	586-38-9	C₈H₈O₃	详情	详情
(XVIII)	51203	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12,15-tris[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl 3-methoxybenzoate		C₄₈H₈₀O₁₁Si₃	详情	详情
(XIX)	51204	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl 3-methoxybenzoate		C₃₆H₅₂O₁₁Si	详情	详情
(XX)	26758	2-(4-methoxyphenyl)acetyl chloride	4693-91-8	C₉H₉ClO₂	详情	详情
(XXI)	51213	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,15-dihydroxy-12-[[2-(4-methoxyphenyl)acetyl]oxy]-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl 3-methoxybenzoate		C₄₅H₆₀O₁₃Si	详情	详情

Extended Information