(2-bromophenyl)(chloro)dimethylsilane -Drug Synthesis Database

【结构式】

【分子编号】55699

【品名】(2-bromophenyl)(chloro)dimethylsilane

【CA登记号】

【分子式】C₈H₁₀BrClSi

【分子量】249.6096

【元素组成】C 38.5% H 4.04% Br 32.01% Cl 14.2% Si 11.25%

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：(IV)

The reaction of FK-506 (I) with Tbdms-Cl and imidazole gives the bis silylated compound (II), which is regioselectively monodesilylated by means of aq. HF in acetonitrile to yield the monosilylated compound (III). The silylation of (III) with 2-bromophenyldimethylsilyl chloride (IV) and imidazole affords the new disilylated compound (V), which is submitted to radical translocating/reducing conditions by means of Et3N/O2 or AIBN as radical initiator and Bu3Sn2H as deuterium source. Under these conditions a mixture of labeled compounds (VI) and (VII) is obtained.

参考文献中间体

合成目标

【1】 Acemoglu, M.; et al.; Regio- and stereoselective preparation of ascomycin-d1 and FK 506-d1. J Label Compd Radiopharm 2002, 45, 5, 361.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI),(VII)	55703	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-17-allyl-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₈H₉₃NO₁₂Si₂	详情	详情
(I)	47057	(1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-allyl-1,14-dihydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethenyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone	C₄₄H₆₉NO₁₂	详情	详情
(II)	55697	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-17-allyl-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₆H₉₇NO₁₂Si₂	详情	详情
(III)	55698	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-17-allyl-14-{[tert-butyl(dimethyl)silyl]oxy}-1-hydroxy-12-{(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethenyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₀H₈₃NO₁₂Si	详情	详情
(IV)	55699	(2-bromophenyl)(chloro)dimethylsilane	C₈H₁₀BrClSi	详情	详情
(V)	55700	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-17-allyl-12-[(E)-2-((1R,3R,4R)-4-{[(2-bromophenyl)(dimethyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-14-{[tert-butyl(dimethyl)silyl]oxy}-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₈H₉₂BrNO₁₂Si₂	详情	详情
(VI)	55701	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-17-allyl-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₈H₉₃NO₁₂Si₂	详情	详情
(VII)	55702	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-17-allyl-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₈H₉₃NO₁₂Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The reaction of ascomycin (I) with Tbdms-Cl and imidazole gives the bis silylated compound (II), which is regioselectively monodesilylated by means of aq. HF in acetonitrile to yield the monosilylated compound (III). The silylation of (III) with 2-bromophenyldimethylsilyl chloride (IV) and imidazole affords the new disilylated compound (V), which is submitted to radical translocating/reducing conditions by means of Et3N/O2 as radical initiator and Bu3Sn2H as deuterium source. Under these conditions a mixture of labeled compounds (VI) and (VII) is obtained where about 70% is the ascomycin labeled compound (VI) and 30% the aromatic labeled compound (VII).

参考文献中间体

合成目标

【1】 Acemoglu, M.; et al.; Regio- and stereoselective preparation of ascomycin-d1 and FK 506-d1. J Label Compd Radiopharm 2002, 45, 5, 361.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI),(VII)	55705	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₇H₉₃NO₁₂Si₂	详情	详情
(I)	14951	(1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethenyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetron	C₄₃H₆₉NO₁₂	详情	详情
(II)	22753	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-[[tert-butyl(dimethyl)silyl]oxy]-12-[(E)-2-((1R,3R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone	C₅₅H₉₇NO₁₂Si₂	详情	详情
(III)	22754	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-[[tert-butyl(dimethyl)silyl]oxy]-17-ethyl-1-hydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethenyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetrone	C₄₉H₈₃NO₁₂Si	详情	详情
(IV)	55699	(2-bromophenyl)(chloro)dimethylsilane	C₈H₁₀BrClSi	详情	详情
(V)	55704	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-12-[(E)-2-((1R,3R,4R)-4-{[(2-bromophenyl)(dimethyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-14-{[tert-butyl(dimethyl)silyl]oxy}-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₇H₉₂BrNO₁₂Si₂	详情	详情
(VI)	55706	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₇H₉₃NO₁₂Si₂	详情	详情
(VII)	55707	(1R,9S,12S,13S,14S,17R,21S,23S,24R,25S,27R)-14-{[tert-butyl(dimethyl)silyl]oxy}-12-[(E)-2-((1R,3R,4R)-4-{[dimethyl(phenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0~4,9~]octacos-18-ene-2,3,10,16-tetrone	C₅₇H₉₃NO₁₂Si₂	详情	详情

Extended Information