Ethyl Acetate → (3S)-2-Oxo-3-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-1-acetic acid methyl ester

HRID 1643379Notes

Reaction equation

HRID 1643379 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]([O:17][C:18]([NH:20][C@@H:21]([CH2:25][NH:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[NH2:33])[C:22]([OH:24])=O)=[O:19])([CH3:16])([CH3:15])[CH3:14].C[CH2:35][O:36][C:37]([CH3:39])=[O:38]>CN(C=O)C>[CH3:35][O:36][C:37](=[O:38])[CH2:39][N:33]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[NH:26][CH2:25][C@H:21]([NH:20][C:18]([O:17][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:19])[C:22]1=[O:24]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22881946(2S)-3-[(2-aminophenyl)amino]-2-{[(tert-butoxy)carbonyl]amino}propanoic acid

Product 1

HCID 54305289(3S)-2-Oxo-3-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-1-acetic acid methyl esterYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(3S)-2-oxo-3-tert-Butoxycarbonylamino-1,3,4,5-tetrahydro-1H-1,5-benzodiazepine. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (8.54 g, 44.5 mmol) was added to a cooled (0° C.) solution of (2S)-2-tert-butoxycarbonylamino-3-(2-aminophenylamino)propionic acid (11.95 g, 40.5 mmol) in 100 ml of DMF and stirred for 18 h. The reaction was poured into 700 ml of EtOAc and washed four times with 100 ml of H2O. The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated to give a brown solid that was purified by flash chromatography eluting with 3:7 EtOAc/hexane to give 8 g (71%) of the title compound: 1H NMR (CDCl3) δ 7.78 (1H, s), 7.02-6.95 (1H, m), 6.88-6.82 (1H, m), 6.82-6.78 (1H, m), 6.75-6.70 (1H, m), 5.8-5.7 (1H, d), 4.55-4.45 (1H, m), 3.95 (1H, s), 3.9-3.82 (1H, m), 3.48-3.40 (1H, m), 1.45 (9H, s).

Workup

  1. washwashed four times with 100 ml of H2O
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customto give a brown solid that
  6. customwas purified by flash chromatography
  7. washeluting with 3:7 EtOAc/hexane

Sources & evidence

ORD record
ord-ca1f8a4e89a54c9cadc06a46d9a362ed
Source dataset
uspto-grants-2012_02
Patent number
US08119631B2

Reaction notes

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