2-[4-[2-methoxy-5-(2-methoxy-2-oxoethyl)phenoxy]phenyl]acetic acid -Drug Synthesis Database

【结构式】

【分子编号】39555

【品名】2-[4-[2-methoxy-5-(2-methoxy-2-oxoethyl)phenoxy]phenyl]acetic acid

【CA登记号】

【分子式】C₁₈H₁₈O₆

【分子量】330.33732

【元素组成】C 65.45% H 5.49% O 29.06%

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：(II)

The condensation of 3,4-methylenedioxy-5-[2-methoxy-4-(N-carbobenzoxyaminoethyl)phenoxy]phenylethylamine (I) with 4-[2-methoxy-5-(methoxycarbonylmethyl)phenoxyphenylacetic acid (II) by means of dicyclohexylcarbodiimide in methylene chloride gives the amide (III), which is hydrolyzed with aqueous Na2CO3 to the corresponding free acid (IV). The cyclization of (IV) by the p-nitrophenyl ester method yields the cyclobisamide (V), which by a Bischler-Napieralski reaction with POCl3 in chloroform is converted into the bis(3,4-dihydroisoquinoline) (VI). The hydrogenation of (VI) with H2 over Pt affords the bis(tetrahydroisoquinoline) derivative (VII), which without isolation is finally methylated with formalin and NaBH4.

参考文献中间体

合成目标

【1】 Tomita, M.; et al.; Synthesis of di-cepharanthine. Tetrahedron Lett 1967, 1201-06.
【2】 Kondo, H.; et al.; US 2206407 .
【3】 Serradell, M.N.; Blancafort, P.; Mealy, N.; Castañer, J.; Cepharanthine. Drugs Fut 1979, 4, 7, 481.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	39554	benzyl 4-[[6-(2-aminoethyl)-1,3-benzodioxol-4-yl]oxy]-3-methoxyphenethylcarbamate	C₂₆H₂₈N₂O₆	详情	详情
(II)	39555	2-[4-[2-methoxy-5-(2-methoxy-2-oxoethyl)phenoxy]phenyl]acetic acid	C₁₈H₁₈O₆	详情	详情
(III)	39556	methyl 2-[3-(4-[2-[(2-[7-[4-(2-[[(benzyloxy)carbonyl]amino]ethyl)-2-methoxyphenoxy]-1,3-benzodioxol-5-yl]ethyl)amino]-2-oxoethyl]phenoxy)-4-methoxyphenyl]acetate	C₄₄H₄₄N₂O₁₁	详情	详情
(IV)	39557	2-[3-(4-[2-[(2-[7-[4-(2-[[(benzyloxy)carbonyl]amino]ethyl)-2-methoxyphenoxy]-1,3-benzodioxol-5-yl]ethyl)amino]-2-oxoethyl]phenoxy)-4-methoxyphenyl]acetic acid	C₄₃H₄₂N₂O₁₁	详情	详情
(V)	39558	22,33-dimethoxy-2,5,7,20-tetraoxa-13,28-diazahexacyclo[29.2.2.2(16,19).1(3,10).1(21,25).0(4,8)]nonatriaconta-1(33),3,8,10(39),16,18,21(38),22,24,31,34,36-dodecaene-14,27-dione	C₃₅H₃₄N₂O₈	详情	详情
(VI)	39559	22,33-dimethoxy-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),13,16,18,21(38),22,24,27,31,34,36-tetradecaene; 22-methoxy-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),13,16,18,21(38),22,24,27,31,34,36-tetradecaen-33-yl methyl ether	C₃₅H₃₀N₂O₆	详情	详情
(VII)	39560	(14S,27R)-22,33-dimethoxy-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),16,18,21(38),22,24,31,34,36-dodecaene; (14S,27R)-22-methoxy-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),16,18,21(38),22,24,31,34,36-dodecaen-33-yl methyl ether	C₃₅H₃₄N₂O₆	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 starting phenylacetic acid (II) is prepared by an Ullman condensation between tert-butyl-4-hydroxyphenylacetate (XVII) and methyl 3-bromo-4-methoxyphenylacetate (XVIII) catalysed by CuO, followed by treatment with p-toluenesulfonic acid in benzene. Compound (XVII) is prepared by esterification of 4-benzyloxyphenylacetic acid (XIX) to the corresponding tart butyl ester (XX), followed by hydrogenolysis with H2 over Pd/C. Compound (XVIII) is prepared by methylation of methyl 3-bromo-4-hydroxyphenylacetate (XXI) with dimethyl sulfate and K2CO3 in DMF.

参考文献中间体

合成目标

【1】 Kondo, H.; et al.; US 2206407 .
【2】 Tomita, M.; et al.; Synthesis of di-cepharanthine. Tetrahedron Lett 1967, 1201-06.
【3】 Serradell, M.N.; Blancafort, P.; Mealy, N.; Castañer, J.; Cepharanthine. Drugs Fut 1979, 4, 7, 481.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	39555	2-[4-[2-methoxy-5-(2-methoxy-2-oxoethyl)phenoxy]phenyl]acetic acid		C₁₈H₁₈O₆	详情	详情
(XVII)	39573	4-hydroxybenzyl pivalate		C₁₂H₁₆O₃	详情	详情
(XVIII)	39575	methyl 2-(3-bromo-4-methoxyphenyl)acetate		C₁₀H₁₁BrO₃	详情	详情
(XIX)	39571	2-[4-(benzyloxy)phenyl]acetic acid	6547-53-1	C₁₅H₁₄O₃	详情	详情
(XX)	39572	4-(benzyloxy)benzyl pivalate		C₁₉H₂₂O₃	详情	详情
(XXI)	39574	methyl 2-(3-bromo-4-hydroxyphenyl)acetate		C₉H₉BrO₃	详情	详情

Extended Information