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【结 构 式】

【分子编号】21199

【品名】(4S)-6-chloro-4-(2-cyclopropylethynyl)-2-(4-methoxyphenyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazine; 4-[(4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-yl]phenyl methyl ether

【CA登记号】

【 分 子 式 】C21H17ClF3NO2

【 分 子 量 】407.8194296

【元素组成】C 61.85% H 4.2% Cl 8.69% F 13.98% N 3.43% O 7.85%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(II)

A new enantioselective synthesis of efavirenz starting from 2-[5-chloro-2-(4-methoxybenzylamino)phenyl]-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2(S)-ol (I), a previously described intermediate [see Drugs Fut 1998 23(2):133], has been reported: The oxidative cyclization of butynol (I) with dichlorodicyanobenzoquinone (DDQ) in toluene gives the benzoxazine (II) which, without isolation, is treated with NaOH and NaBH4 in methanol yielding the aminoalcohol (III). The acylation of (III) with methyl chloroformate (IV) and NaHCO3 in water affords the carbamate (V). Finally, this compound is cyclized by means of lithium tert-butoxide in tert-butyl methyl ether, or KOH in tert-butyl methyl ether/water.

1 Pierce, M.E.; et al.; Practical asymmetric synthesis of efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor. J Org Chem 1998, 63, 23, 8536.
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) 16578 (2S)-2-[5-chloro-2-[(4-methoxybenzyl)amino]phenyl]-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol C21H19ClF3NO2 详情 详情
(II) 21199 (4S)-6-chloro-4-(2-cyclopropylethynyl)-2-(4-methoxyphenyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazine; 4-[(4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-yl]phenyl methyl ether C21H17ClF3NO2 详情 详情
(III) 21200 (2S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol 209414-27-7 C13H11ClF3NO 详情 详情
(IV) 16993 methyl chlorocarbonate;Carbonochloridic acid methyl ester;[(chlorocarbonyl)oxy]methane;methyl chloroformate 79-22-1 C2H3ClO2 详情 详情
(V) 21204 methyl 4-chloro-2-[(1S)-3-cyclopropyl-1-hydroxy-1-(trifluoromethyl)-2-propynyl]phenylcarbamate C15H13ClF3NO3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(II)

A new enantioselective synthesis of efavirenz starting from 2-[5-chloro-2-(4-methoxybenzylamino)phenyl]-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2(S)-ol (I), a previously described intermediate [see Drugs Fut 1998 23(2):133], has been reported: The oxidative cyclization of butynol (I) with dichlorodicyanobenzoquinone (DDQ) in toluene gives the benzoxazine (II) which, without isolation, is treated with NaOH and NaBH4 in methanol yielding the aminoalcohol (III). The acylation of (III) with p-nitrophenyl chloroformate (IV) and NaHCO3 in water affords the carbamate (V). Finally, this compound is cyclized by means of lithium tert-butoxide in tert-butyl methyl ether, or KOH in tert-butyl methyl ether/water.

1 Pierce, M.E.; et al.; Practical asymmetric synthesis of efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor. J Org Chem 1998, 63, 23, 8536.
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) 16578 (2S)-2-[5-chloro-2-[(4-methoxybenzyl)amino]phenyl]-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol C21H19ClF3NO2 详情 详情
(II) 21199 (4S)-6-chloro-4-(2-cyclopropylethynyl)-2-(4-methoxyphenyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazine; 4-[(4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-yl]phenyl methyl ether C21H17ClF3NO2 详情 详情
(III) 21200 (2S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol 209414-27-7 C13H11ClF3NO 详情 详情
(IV) 16605 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene 7693-46-1 C7H4ClNO4 详情 详情
(V) 21203 4-nitrophenyl 4-chloro-2-[(1S)-3-cyclopropyl-1-hydroxy-1-(trifluoromethyl)-2-propynyl]phenylcarbamate C20H14ClF3N2O5 详情 详情
Extended Information