(1R,3R)-5-(4-hydroxy-5-methoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol -Drug Synthesis Database

【结构式】

【分子编号】38308

【品名】(1R,3R)-5-(4-hydroxy-5-methoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol

【CA登记号】

【分子式】C₂₃H₂₅NO₄

【分子量】379.45584

【元素组成】C 72.8% H 6.64% N 3.69% O 16.87%

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：(S-biar)

The condensation of the isoquinoline intermediate (IX) with the naphthaleneboronic acid intermediate (XIX) by means of palladium tetrakis(triphenylphosphine) and NaHCO3 in refluxing ethanol/toluene gives a 5:4 mixture of the (S) and (R) atropaisomers (XXIII), which, without separation, are treated with methanolic HCl to eliminate the methoxymethyl protecting groups and yield a mixture of (S) and (R) (XXIV). The debenzylation of this mixture by means of H2 over Pd/C in methanol/dichloromethane affords a mixture of the target (S-biar) compound, along with its (R-biar)-atropaisomer that are separated by HPLC.

参考文献中间体

合成目标

【1】 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(S)-(XXIV)	37861	4-[(1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-8-methoxy-6-methyl-1-naphthol	C₄₄H₄₃NO₄	详情	详情
(S-biar)	38308	(1R,3R)-5-(4-hydroxy-5-methoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol	C₂₃H₂₅NO₄	详情	详情
(S)-(XXIII)	38319	(1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-(4,5-dimethoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline; benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-(4,5-dimethoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether	C₄₆H₄₇NO₅	详情	详情
(R)-(XXIII)	63435	2-benzyl-6,8-bis(benzyloxy)-5-[5-methoxy-4-(methoxymethoxy)-7-methyl-1-naphthyl]-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline; benzyl 2-benzyl-6-(benzyloxy)-5-[5-methoxy-4-(methoxymethoxy)-7-methyl-1-naphthyl]-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether	C₄₆H₄₇NO₅	详情	详情
(R)-(XXIV)	63438	4-{1,3-dimethyl-2-(phenylmethyl)-6,8-bis[(phenylmethyl)oxy]-1,2,3,4-tetrahydro-5-isoquinolinyl}-6-methyl-8-(methyloxy)-1-naphthalenol	C₄₄H₄₃NO₄	详情	详情
(IX)	37847	benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline	C₃₂H₃₂INO₂	详情	详情
(XIX)	37856	5-methoxy-4-(methoxymethoxy)-7-methyl-1-naphthylboronic acid	C₁₄H₁₇BO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(R-biar)

The condensation of the isoquinoline intermediate (IX) with the naphthaleneboronic acid intermediate (XIX) by means of palladium tetrakis(triphenylphosphine) and NaHCO3 in refluxing ethanol/toluene gives a 5:4 mixture of the (S) and (R) atropaisomers (XXIII), which, without separation, are treated with methanolic HCl to eliminate the methoxymethyl protecting groups and yield a mixture of (S) and (R) (XXIV). The debenzylation of this mixture by means of H2 over Pd/C in methanol/dichloromethane affords a mixture of the target (R-biar) compound, along with its (S-biar)-atropaisomer that are separated by HPLC.

参考文献中间体

合成目标

【1】 Hoye, T.R.; et al.; Total synthesis of michellamines A-C, korupensamines A-D, and ancistrobrevine B. J Org Chem 1999, 64, 19, 7184.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(S)-(XXIV)	37861	4-[(1R,3R)-2-benzyl-6,8-bis(benzyloxy)-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-8-methoxy-6-methyl-1-naphthol	C₄₄H₄₃NO₄	详情	详情
(R-biar)	38308	(1R,3R)-5-(4-hydroxy-5-methoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol	C₂₃H₂₅NO₄	详情	详情
(S)-(XXIII)	38319	(1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-(4,5-dimethoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline; benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-(4,5-dimethoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether	C₄₆H₄₇NO₅	详情	详情
(R)-(XXIII)	63435	2-benzyl-6,8-bis(benzyloxy)-5-[5-methoxy-4-(methoxymethoxy)-7-methyl-1-naphthyl]-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline; benzyl 2-benzyl-6-(benzyloxy)-5-[5-methoxy-4-(methoxymethoxy)-7-methyl-1-naphthyl]-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether	C₄₆H₄₇NO₅	详情	详情
(R)-(XXIV)	63438	4-{1,3-dimethyl-2-(phenylmethyl)-6,8-bis[(phenylmethyl)oxy]-1,2,3,4-tetrahydro-5-isoquinolinyl}-6-methyl-8-(methyloxy)-1-naphthalenol	C₄₄H₄₃NO₄	详情	详情
(IX)	37847	benzyl (1R,3R)-2-benzyl-6-(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydro-8-isoquinolinyl ether; (1R,3R)-2-benzyl-6,8-bis(benzyloxy)-5-iodo-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline	C₃₂H₃₂INO₂	详情	详情
(XIX)	37856	5-methoxy-4-(methoxymethoxy)-7-methyl-1-naphthylboronic acid	C₁₄H₁₇BO₅	详情	详情

Extended Information