Phosphorus oxychloride → tert-butyl(2S,3S)-8-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

HRID 1486085ノート

反応式

HRID 1486085 の反応式
[C:1]([C:3]1[CH:23]=[CH:22][C:6]2[NH:7][C:8](=[O:21])[C@@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[C@H:10]([CH3:12])[NH:11][C:5]=2[CH:4]=1)#[N:2].[CH3:24][S:25]([CH2:28][C:29](O)=[O:30])(=[O:27])=[O:26].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[C:1]([C:3]1[CH:23]=[CH:22][C:6]2[NH:7][C:8](=[O:21])[C@@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:18])([CH3:19])[CH3:17])[C@H:10]([CH3:12])[N:11]([C:29](=[O:30])[CH2:28][S:25]([CH3:24])(=[O:27])=[O:26])[C:5]=2[CH:4]=1)#[N:2]

参加物

5

反応物 3

HCID 24813Phosphorus oxychlorideHCID 37328412-Methanesulfonylacetic acidHCID 72713838Tert-butyl ((3S,4S)-7-cyano-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[B][1,4]diazepin-3-YL)carbamate

生成物 1

HCID 72713839tert-butyl(2S,3S)-8-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate収率 94%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
0 °C

実験手順

To a 0° C. solution of tert-butyl(3S,4S)-7-cyano-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (106 mg, 335 μmol) in pyridine (3.35 ml) was added 2-(methylsulfonyl)acetic acid (50.9 mg, 369 μmol) followed by phosphoryl chloride (61.3 μl, 670 μmol), dropwise. The reaction was stirred at 0° C. for 30 min, then quenched by the addition of H2O and extracted with EtOAc. The combined organic layers were washed with 1 N aq. citric acid, H2O, sat. aq. NaHCO3, and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(2S,3S)-8-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (137 mg, 94%) as a white solid. MS m/z 459 (MNa)+.

後処理

  1. customquenched by the addition of H2O
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with 1 N aq. citric acid, H2O, sat. aq. NaHCO3, and sat. aq. NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by flash chromatography

出典と根拠

ORDレコード
ord-cee334142b074ceaadd0c998f737117c
出典データセット
uspto-grants-2016_08
特許番号
US09422331B2

反応ノート

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