1,1'-Carbonyldiimidazole → methyl 2-((R)-(3-fluorophenyl)((3R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-(tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate

HRID 452017ノート

反応式

HRID 452017 の反応式
[NH2:1][C@@H:2]([CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][O:18][CH2:17]1)[CH2:3][N:4]([CH3:14])[C:5](=[O:13])[O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10].C1N=CN([C:27]([N:29]2[CH:33]=N[CH:31]=[CH:30]2)=[O:28])C=1.CCN(C(C)C)C(C)C.[CH3:43][O:44][C:45](=[O:64])[NH:46][CH2:47][CH2:48][O:49][CH:50]([C:57]1[CH:62]=[CH:61][CH:60]=[C:59]([F:63])[CH:58]=1)[CH:51]1CCCN[CH2:52]1>C(Cl)Cl>[F:63][C:59]1[CH:58]=[C:57]([C@@H:50]([C@@H:51]2[CH2:52][CH2:31][CH2:30][N:29]([C:27](=[O:28])[NH:1][C@@H:2]([CH2:15][CH:16]3[CH2:21][CH2:20][CH2:19][O:18][CH2:17]3)[CH2:3][N:4]([C:5]([O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10])=[O:13])[CH3:14])[CH2:33]2)[O:49][CH2:48][CH2:47][NH:46][C:45](=[O:64])[O:44][CH3:43])[CH:62]=[CH:61][CH:60]=1

参加物

6

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 67365379{2-[(3-Fluoro-phenyl)-piperidin-3-yl-methoxy]-ethyl}-carbamic acid methyl esterHCID 673661002-(trimethylsilyl)ethyl (S)-2-amino-3-(tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate

生成物 1

HCID 67365837methyl 2-((R)-(3-fluorophenyl)((3R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-(tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate収率 50%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of 2-(trimethylsilyl)ethyl (S)-2-amino-3-(tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate (300 mg, 0.95 mmol) and CDI (154 mg, 0.95 mmol) in anhydrous CH2Cl2 (20 mL), DIEA (612 mg, 4.7 mmol) was added with ice bath. After addition, the mixture was stirred for 1 h at 0° C., then was added to a solution of {2-[(3-fluoro-phenyl)-piperidin-3-yl-methoxy]-ethyl}-carbamic acid methyl ester (245 mg, 0.79 mmol) in anhydrous CH2Cl2 (25 mL). The reaction mixture was allowed to warm to rt and stirred overnight. After the reaction was completed, the solvent was removed in vacuo. The product was purified by preparative TLC to afford methyl 2-((R)-(3-fluorophenyl)((3R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-(tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (258 mg, 50% yield).

後処理

  1. additionAfter addition
  2. temperatureto warm to rt
  3. stirringstirred overnight
  4. customthe solvent was removed in vacuo
  5. customThe product was purified by preparative TLC

出典と根拠

ORDレコード
ord-d56fe6c0cd0842a4bb343eaf5e3fe4d3
出典データセット
uspto-grants-2013_07
特許番号
US08487108B2

反応ノート

読み込み中…