4-Methylmorpholine → N2-[(3,5-difluorophenyl)acetyl]-N1-[(3S,7S)-1-methyl-2-oxo-7-phenylazepan-3-yl]-L-alaninamide

HRID 1392071Notes

Reaction equation

HRID 1392071 reaction equation
[NH2:1][C@H:2]1[CH2:8][CH2:7][CH2:6][C@@H:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:4]([CH3:15])[C:3]1=[O:16].[F:17][C:18]1[CH:19]=[C:20]([CH2:25][C:26]([NH:28][C@H:29]([C:31](O)=[O:32])[CH3:30])=[O:27])[CH:21]=[C:22]([F:24])[CH:23]=1.CCN=C=NCCCN(C)C.Cl.CN1CCOCC1>C(Cl)Cl>[F:17][C:18]1[CH:19]=[C:20]([CH2:25][C:26]([NH:28][C@H:29]([C:31]([NH:1][C@H:2]2[CH2:8][CH2:7][CH2:6][C@@H:5]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[N:4]([CH3:15])[C:3]2=[O:16])=[O:32])[CH3:30])=[O:27])[CH:21]=[C:22]([F:24])[CH:23]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9990953(3S,7S)-3-amino-1-methyl-7-phenylazepan-2-oneHCID 12135350(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoic acid

Product 1

HCID 10433508N2-[(3,5-difluorophenyl)acetyl]-N1-[(3S,7S)-1-methyl-2-oxo-7-phenylazepan-3-yl]-L-alaninamideYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3S,7S)-3-amino-1-methyl-7-phenylazepan-2-one (2e) (57 mg) in DCM (3 mL) at 0° C. under N2 was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (95 mg), HOBt-hydrate (88 mg), EDAC.HCl (75 mg) and N-methyl morpholine (42 mg). The reaction mixture was stirred 1 h at 0° C. and 3H at room temperature, 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 (2% MeOH/DCM) to afford the title compound as an off-white solid (80 mg, 70%). 1H NMR (300 MHz, CDCl3) δ 1.40 (d, 3H), 1.51 (m, 1H), 1.90-2.01 (m, 3H), 2.12-2.15 (m, 2H), 2.52 (s, 3H), 3.55 (s, 2H), 4.47-4.56 (m, 1H), 4.92-5.00 (m, 2H), 6.29 (bd, 1H), 6.69-6.76 (m, 1H), 6.84 (bd, 2H), 7.27-7.41 (m, 6H). MS APCI, m/z=444 (M+1)/466 (M+Na). LC/MS 2.54 min., Method A.

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 (2% MeOH/DCM)

Sources & evidence

ORD record
ord-bd994b25f76644228e86f6531852897e
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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