• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】36612

【品名】6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-3,4-dihydro-2(1H)-quinazolinone

【CA登记号】

【 分 子 式 】C14H10ClF3N2O

【 分 子 量 】314.6941896

【元素组成】C 53.43% H 3.2% Cl 11.27% F 18.11% N 8.9% O 5.08%

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:(V)

Condensation of 2'-amino-5'-chloro-2,2,2-trifluoroacetophenone (I) with trimethylsilyl isocyanate in the presence of dimethylaminopyridine, followed by desilylation with tetrabutylammonium fluoride provided the quinazoline derivative (II). Dehydration of the tertiary alcohol of (II) to afford imine (III) was carried out employing molecular sieves in refluxing toluene. Subsequent addition of lithium cyclopropylacetylide (IV) to (III) in the presence of BF3-Et2O yielded the racemic adduct (V). The desired (S)-enantiomer was finally isolated by means of chiral HPLC.

1 Rodgers, J.D.; Koo, S.S.; Corbett, J.W.; et al.; Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1. Antimicrob Agents Chemother 1999, 43, 12, 2893.
2 Corbett, J.W.; Ko, S.S.; Rodgers, J.D.; et al.; Inhibition of clinically relevant mutant variant of HIV-1 by quinazolinone non-nucleoside reverse transcriptase inhibitors. J Med Chem 2000, 43, 10, 2019.
3 Corbett, J.W.; Ko, S.S. (DuPont Pharmaceuticals Co.); 4,4-Disubstd.-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors. US 6124302; WO 9845276 .
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) 16572 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoro-1-ethanone C8H5ClF3NO 详情 详情
(II) 36609 6-chloro-4-hydroxy-4-(trifluoromethyl)-3,4-dihydro-2(1H)-quinazolinone C9H6ClF3N2O2 详情 详情
(III) 36610 6-chloro-4-(trifluoromethyl)-2(1H)-quinazolinone C9H4ClF3N2O 详情 详情
(IV) 36611 (2-cyclopropylethynyl)lithium C5H5Li 详情 详情
(V) 36612 6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-3,4-dihydro-2(1H)-quinazolinone C14H10ClF3N2O 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

Condensation of 2'-amino-5'-chloro-2,2,2-trifluoroacetophenone (I) with trimethylsilyl isocyanate in the presence of dimethylaminopyridine, followed by desilylation with tetrabutylammonium fluoride provided the quinazoline derivative (II). Dehydration of the tertiary alcohol of (II) to afford imine (III) was carried out employing molecular sieves in refluxing toluene. Subsequent addition of lithium cyclopropylacetylide (IV) to (III) in the presence of BF3-Et2O yielded the racemic adduct (V). The desired (S)-enantiomer (VI) was then isolated by means of chiral HPLC. Finally, reduction of the triple bond of (VI) with LiAlH4 furnished the corresponding olefin.

1 Corbett, J.W.; Ko, S.S.; Rodgers, J.D.; et al.; Inhibition of clinically relevant mutant variant of HIV-1 by quinazolinone non-nucleoside reverse transcriptase inhibitors. J Med Chem 2000, 43, 10, 2019.
2 Rodgers, J.D.; Koo, S.S.; Corbett, J.W.; et al.; Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1. Antimicrob Agents Chemother 1999, 43, 12, 2893.
3 Corbett, J.W.; Ko, S.S. (DuPont Pharmaceuticals Co.); 4,4-Disubstd.-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors. US 6124302; WO 9845276 .
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) 16572 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoro-1-ethanone C8H5ClF3NO 详情 详情
(II) 36609 6-chloro-4-hydroxy-4-(trifluoromethyl)-3,4-dihydro-2(1H)-quinazolinone C9H6ClF3N2O2 详情 详情
(III) 36610 6-chloro-4-(trifluoromethyl)-2(1H)-quinazolinone C9H4ClF3N2O 详情 详情
(IV) 36611 (2-cyclopropylethynyl)lithium C5H5Li 详情 详情
(V) 36612 6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-3,4-dihydro-2(1H)-quinazolinone C14H10ClF3N2O 详情 详情
(VI) 36613 (4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-3,4-dihydro-2(1H)-quinazolinone C14H10ClF3N2O 详情 详情
Extended Information