3-(Tert-butyldimethylsilyloxy)-2,2-dimethylpropyl methanesulfonate → tert-butyl (2S,4S)-4-{[6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl]sulfanyl}-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidine-1-carboxylate

HRID 906470ノート

反応式

HRID 906470 の反応式
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH:6]=[C:5]2[S:13][C@H:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:16]([CH2:27][O:28][Si:29]([C:42]([CH3:45])([CH3:44])[CH3:43])([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:15]1.CS(O[CH2:51][C:52]([CH3:63])([CH3:62])[CH2:53][O:54][Si:55]([C:58]([CH3:61])([CH3:60])[CH3:59])([CH3:57])[CH3:56])(=O)=O>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:51][C:52]([CH3:63])([CH3:62])[CH2:53][O:54][Si:55]([C:58]([CH3:61])([CH3:60])[CH3:59])([CH3:56])[CH3:57])[CH:6]=[C:5]2[S:13][C@H:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[C@H:16]([CH2:27][O:28][Si:29]([C:42]([CH3:45])([CH3:44])[CH3:43])([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:15]1

参加物

3

反応物 2

HCID 574399153-(Tert-butyldimethylsilyloxy)-2,2-dimethylpropyl methanesulfonateHCID 86640978tert-Butyl (2S,4S)-4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidine-1-carboxylate

生成物 1

HCID 86640980tert-butyl (2S,4S)-4-{[6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl]sulfanyl}-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidine-1-carboxylate収率 99.7%

実験手順

tert-Butyl (2S,4S)-4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidine-1-carboxylate (Example 67e, 0.68 g) and 3-(tert-butyldimethylsilyloxy)-2,2-dimethylpropyl methanesulfonate (0.315 g) were reacted by the method of Example 58c to afford crude tert-butyl (2S,4S)-4-{[6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl]sulfanyl}-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidine-1-carboxylate (0.87 g) as a colourless oil. This was reacted with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.306 g) by the method of Example 58d to afford tert-butyl (2S,4S)-4-({2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-6-[5-(cyclo-ropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl}sulfanyl)-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidine-1-carboxylate as a colourless oil. This was diluted in ethanol (3 mL) and treated with 4M HCl in dioxane (1 mL) and stirred at room temperature for 20 h. The volatiles were removed in vacuo. The crude material was dissolved in methanol (2 mL) and loaded on to a 10 g SCX cartridge. The impurities were washed through with methanol (50 mL) and discarded. The product was eluted with 1N methanolic ammonia (75 mL) and the solvents evaporated in vacuo. Purification by preparative HPLC (Gemini-NX C18 column using a 95-5% gradient of aqueous 0.1% ammonia in methanol as eluent) afforded the title compound (32 mg) as a white solid.

出典と根拠

ORDレコード
ord-649a89697d294cb697bae5064fde7b82
出典データセット
uspto-grants-2011_09
特許番号
US08012980B2

反応ノート

読み込み中…