Diisopropylethylamine → tert-Butyl methyl((S)-1-oxo-1-((S)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)propan-2-yl)carbamate

HRID 1055360Notes

Reaction equation

HRID 1055360 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@H:9]1[CH2:15][O:14][C:13]2[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=2[NH:11][C:10]1=[O:20].[C:21]([O:25][C:26]([N:28]([CH3:34])[C@@H:29]([CH3:33])[C:30](O)=[O:31])=[O:27])([CH3:24])([CH3:23])[CH3:22].O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.CCOC(C)=O>[CH3:34][N:28]([C@@H:29]([CH3:33])[C:30](=[O:31])[NH:8][C@H:9]1[CH2:15][O:14][C:13]2[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=2[NH:11][C:10]1=[O:20])[C:26](=[O:27])[O:25][C:21]([CH3:24])([CH3:22])[CH3:23]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 69197641(S)-3-amino-2,3-dihydrobenzo[b][1,4]oxazepin-4(5H)-one trifluoroacetate

Product 1

HCID 72713380tert-Butyl methyl((S)-1-oxo-1-((S)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)propan-2-yl)carbamateYield 84.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (S)-3-amino-2,3-dihydrobenzo[b][1,4]oxazepin-4(5H)-one trifluoroacetate (500 mg, 1.71 mmol, Eq: 1.00), (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (348 mg, 1.71 mmol, Eq: 1.00), O-benzotriazol-1-yl-N,N,N′N′-tetramethyluronium hexafluorophosphate (HBTU, 682 mg, 1.8 mmol, Eq: 1.05) and 1-hydroxybenzotriazole hydrate (HOBT120, 243 mg, 1.8 mmol, Eq: 1.05) in DMF (5 mL) was added N,N-diisopropylethylamine (DIEA, 553 mg, 4.28 mmol, Eq: 2.50). The mixture was stirred for 45 min., diluted with 50 mL EtOAc and washed H2O, 2% KHSO4, 5% NaHCO3 and 5% brine. The organic solution was dried over Na2SO4, filtered and concentrated to give the title compound (525 mg, 84%) as a tan foam which was used without purification.

Workup

  1. washwashed H2O, 2% KHSO4, 5% NaHCO3 and 5% brine
  2. dry with materialThe organic solution was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-9cd85fcc05ac48ba87df9c2a490f77dc
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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