Dimethylformamide → tert-butyl(2S,3S)-7-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

HRID 1486076ノート

反応式

HRID 1486076 の反応式
Br[C:2]1[CH:29]=[CH:28][C:5]2[N:6]([C:21](=[O:27])[CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[C@@H:7]([CH3:20])[C@H:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:9](=[O:11])[NH:10][C:4]=2[CH:3]=1.[CH3:30][N:31](C=O)C>[C-]#N.[Zn+2].[C-]#N>[C:30]([C:2]1[CH:29]=[CH:28][C:5]2[N:6]([C:21](=[O:27])[CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[C@@H:7]([CH3:20])[C@H:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:16])[CH3:17])[C:9](=[O:11])[NH:10][C:4]=2[CH:3]=1)#[N:31]

参加物

4

反応物 2

HCID 6228DimethylformamideHCID 131736774tert-butyl(2S,3S)-7-bromo-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

生成物 1

HCID 131736775tert-butyl(2S,3S)-7-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 11186Zinc cyanide (Zn(CN)2)触媒

反応条件

温度
110 °C

実験手順

A solution of tert-butyl(2S,3S)-7-bromo-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (124 mg, 253 μmol) in DMF (2.53 ml) was sparged with Ar for 10 min, then zinc cyanide (59.4 mg, 506 μmol) and tetrakis(triphenyl-phosphine)palladium(0) (29.2 mg, 25.3 μmol) were added. The mixture was sparged with Ar for an additional 5 min, then sealed and heated in the microwave at 110° C. for 20 min, then diluted with H2O and extracted with EtOAc. The combined organic layers were washed with H2O and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(2S,3S)-7-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (104 mg, 94%) as a white solid. MS m/z 459 (MNa)+.

後処理

  1. customThe mixture was sparged with Ar for an additional 5 min
  2. customsealed
  3. additiondiluted with H2O
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with H2O and sat. aq. NaCl
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by flash chromatography

出典と根拠

ORDレコード
ord-16098328f528415aa9a554c3f1ee4001
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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