Diisopropylethylamine → {(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester

HRID 1486036Notes

Reaction equation

HRID 1486036 reaction equation
Cl.[C:2]([C:5]1[CH:26]=[CH:25][C:8]([C:9]([N:11]2[C@@H:17]([CH3:18])[C@H:16]([NH2:19])[C:15](=[O:20])[NH:14][C:13]3[CH:21]=[CH:22][CH:23]=[CH:24][C:12]2=3)=[O:10])=[CH:7][CH:6]=1)(=[O:4])[CH3:3].[C:27]([O:31][C:32]([N:34]([CH3:40])[C@@H:35]([CH3:39])[C:36](O)=[O:37])=[O:33])([CH3:30])([CH3:29])[CH3:28].C(N(CC)C(C)C)(C)C>CN(C)C=O.O>[C:27]([O:31][C:32](=[O:33])[N:34]([C@H:35]([C:36](=[O:37])[NH:19][C@H:16]1[C@H:17]([CH3:18])[N:11]([C:9](=[O:10])[C:8]2[CH:25]=[CH:26][C:5]([C:2](=[O:4])[CH3:3])=[CH:6][CH:7]=2)[C:12]2[CH:24]=[CH:23][CH:22]=[CH:21][C:13]=2[NH:14][C:15]1=[O:20])[CH3:39])[CH3:40])([CH3:28])([CH3:29])[CH3:30]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 90082607(3S,4S)-5-(4-acetyl-benzoyl)-3-amino-4-methyl-1,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2-one hydrochloride

Product 1

HCID 90082668{(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (3S,4S)-5-(4-acetyl-benzoyl)-3-amino-4-methyl-1,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2-one hydrochloride (0.39 g, 1.03 mmol) in N,N-dimethylformamide (6.0 mL) at 0° C. was added (S)-2-(tert-butoxycarbonyl-methyl-amino)-propionic acid (0.23 g, 1.13 mmol), N,N-diisopropylethylamine (0.72 mL, 4.12 mmol) and 0-benzotriazol-1-yl-N,N,N′N′-tetramethyluronium hexafluorophosphate (0.43 g, 1.13 mmol), the reaction was stirred for 2 h. The reaction mixture was diluted with water (50 ml) and extracted with ethyl acetate (2×40 mL). The organic layers were combined, washed with a saturated aqueous solution of sodium hydrogen carbonate (1×20 mL), water (1×25 mL), dried over sodium sulfate, filtered through a plug of silica gel and concentrated in vacuo to give {(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester which was used in the subsequent step without further purification (0.53 g, 98%).

Workup

  1. extractionextracted with ethyl acetate (2×40 mL)
  2. washwashed with a saturated aqueous solution of sodium hydrogen carbonate (1×20 mL), water (1×25 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered through a plug of silica gel
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-87633d7ce81745da8e738289fb3dde7d
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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