4-Methylmorpholine → N1-[(3S,7S)-benzyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]-N2-[(3,5-difluorophenyl)acetyl]-L-alaninamide

HRID 1392086Notes

Reaction equation

HRID 1392086 reaction equation
[NH2:1][C@H:2]1[CH2:8][CH:7]=[CH:6][C@@H:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:4]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:3]1=[O:22].[F:23][C:24]1[CH:25]=[C:26]([CH2:31][C:32]([NH:34][C@H:35]([C:37](O)=[O:38])[CH3:36])=[O:33])[CH:27]=[C:28]([F:30])[CH:29]=1.CCN=C=NCCCN(C)C.Cl.CN1CCOCC1>C(Cl)Cl>[CH2:15]([N:4]1[C@H:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:7][CH2:8][C@H:2]([NH:1][C:37](=[O:38])[C@H:35]([CH3:36])[NH:34][C:32](=[O:33])[CH2:31][C:26]2[CH:27]=[C:28]([F:30])[CH:29]=[C:24]([F:23])[CH:25]=2)[C:3]1=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12135350(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoic acidHCID 58691185(3S,7S)-3-amino-1-benzyl-7-phenyl-1,3,4,7-tetrahydro-2H-azepin-2-one

Product 1

HCID 10459239N1-[(3S,7S)-benzyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]-N2-[(3,5-difluorophenyl)acetyl]-L-alaninamideYield 71.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3S,7S)-3-amino-1-benzyl-7-phenyl-1,3,4,7-tetrahydro-2H-azepin-2-one (5d) (40 mg) in DCM (2 mL) at 0° C. under N2 was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (33 mg), HOBt-hydrate (46 mg), EDAC.HCl (39 mg) and N-methyl morpholine (22 mg). The reaction mixture was stirred 1 h at 0° C. and 3 h at RT, then diluted with 30% hexanes/EtOAc (100 mL). The organic phase was consecutively washed with H2O, 0.2 N HCl, saturated NaHCO3, and brine, dried (Na2SO4), filtered and evaporated. The crude product was purified by flash chromatography (1%-2% MeOH/DCM) to afford a white solid (50 mg, 71%). Sample contains approx. 20% 5A.

Workup

  1. washThe organic phase was consecutively washed with H2O, 0.2 N HCl, saturated NaHCO3, and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified by flash chromatography (1%-2% MeOH/DCM)

Sources & evidence

ORD record
ord-8bb3afbd8b0a4ee981ff7885793c7c23
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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