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 1486076Notes

Reaction equation

HRID 1486076 reaction equation
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]

Participants

4

Reactant 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

Product 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-ylcarbamateYield 94%

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
110 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-16098328f528415aa9a554c3f1ee4001
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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