1-Methylimidazole → Tert-butyl ((3S,4S)-7-cyano-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[B][1,4]diazepin-3-YL)carbamate

HRID 1486084Notes

Reaction equation

HRID 1486084 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][C:3]=1[NH:10][C@@H:11]([CH3:24])[C@H:12]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:13](O)=[O:14].CN1C=CN=C1.CS(Cl)(=O)=O>C(#N)C>[C:8]([C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:13](=[O:14])[C@@H:12]([NH:16][C:17](=[O:18])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C@H:11]([CH3:24])[NH:10][C:3]=2[CH:4]=1)#[N:9]

Participants

5

Reactant 3

HCID 13901-MethylimidazoleHCID 31297Methanesulfonyl chlorideHCID 72712568(2S,3S)-3-(2-amino-5-cyanophenylamino)-2-(tert-butoxycarbonylamino)butanoic acid

Product 1

HCID 72713838Tert-butyl ((3S,4S)-7-cyano-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[B][1,4]diazepin-3-YL)carbamateYield 90.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (2S,3S)-3-(2-amino-5-cyanophenylamino)-2-(tert-butoxycarbonylamino)butanoic acid (4.9 g, 14.7 mmol) in acetonitrile (96 ml), was cooled in an ice water bath, then 1-methylimidazole (3.5 ml, 44.0 mmol) was added and the reaction was stirred at 0° C. for 20 min, then methanesulfonyl chloride (1.31 ml, 16.9 mmol) was added dropwise. The cooling bath was removed and the reaction was stirred at RT for 2 h, then concentrated to 13 volume and treated with water (˜200 ml, dropwise addition). The resulting solid was separated by filtration, washed with H2O, and dried under vacuum at 50° C. for 3 h to afford tert-butyl(3S,4S)-7-cyano-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (4.2 g). The aqueous solution was extracted with EtOAc, dried over Na2SO4, and purified by flash chromatography (0-60% EtOAc in DCM) to afford additional product (0.4 g). MS m/z 339 (MNa)+.

Workup

  1. temperaturewas cooled in an ice water bath
  2. customThe cooling bath was removed
  3. stirringthe reaction was stirred at RT for 2 h
  4. concentrationconcentrated to 13 volume
  5. additiontreated with water (
  6. addition˜200 ml, dropwise addition)
  7. customThe resulting solid was separated by filtration
  8. washwashed with H2O
  9. customdried under vacuum at 50° C. for 3 h

Sources & evidence

ORD record
ord-160dca2a5774482c914a290102d8c665
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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