Diisopropylethylamine → tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1486089Notes

Reaction equation

HRID 1486089 reaction equation
[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:19])OC(C)(C)C)[C:8](=[O:20])[NH:7][C:6]2[CH:21]=[CH:22][C:23]([C:25]#[N:26])=[CH:24][C:5]1=2)(=[O:3])[CH3:2].[C:27]([N:34]([CH3:40])[C@H:35](C(O)=O)[CH3:36])([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>Cl.O1CCOCC1.CCOCC.CCOC(C)=O>[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:19])[C@@H:35]([N:34]([CH3:40])[C:27](=[O:28])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])[CH3:36])[C:8](=[O:20])[NH:7][C:6]2[CH:21]=[CH:22][C:23]([C:25]#[N:26])=[CH:24][C:5]1=2)(=[O:3])[CH3:2]

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 131736779tert-butyl(2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

Product 1

HCID 90088957tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 69%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A rt solution of tert-butyl(2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (144 mg, 402 μmol) in 4 M HCl in dioxane (2.01 ml) was stirred for 2 h. The reaction was diluted with Et2O and the solids were collected by vacuum filtration, taken up in DMF (1.34 ml), and Boc-N-methyl-L-alanine (89.9 mg, 442 μmol), N,N-diisopropylethylamine (278 μl, 1.61 mmol), and HBTU (168 mg, 442 μmol) were added at 0° C. The reaction was stirred at rt for 30 min, then diluted with EtOAc, washed with H2O, sat. aq. NaHCO3, and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (123 mg, 69%) as a white solid. MS m/z 466 (MNa)+.

Workup

  1. filtrationthe solids were collected by vacuum filtration
  2. washwashed with H2O, sat. aq. NaHCO3, and sat. aq. NaCl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-86b18467d4bd4c968caad427cf8768f5
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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