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

HRID 1392069Notes

Reaction equation

HRID 1392069 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]([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][CH:7]=[CH: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 10242432(3S,7S)-3-amino-1-methyl-7-phenyl-1,3,4,7-tetrahydro-2H-azepin-2-oneHCID 12135350(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoic acid

Product 1

HCID 9889500N2-[(3,5-difluorophenyl)acetyl]-N1-[(3S,7S)-1-methyl-2-oxo-7-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-yl]-L-alaninamideYield 19%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3S,7S)-3-amino-1-methyl-7-phenyl-1,3,4,7-tetrahydro-2H-azepin-2-one (1f) (120 mg) in DCM (6 mL) at 0° C. under N2 was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (135 mg), HOBt-hydrate (186 mg), EDAC.HCl (160 mg) and N-methyl morpholine (92 mg). The reaction mixture was stirred 1 h at 0° C. and 2.5 h 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 (1% MeOH/DCM) to afford the title compound as an off-white solid (45 mg, 19%). 1H NMR (300 MHz, CDCl3) δ 1.41 (d, 3H), 2.18-2.29 (m, 1H), 2.54 (s, 3H), 2.79-2.87 (m, 1H), 3.55 (s, 2H), 4.47-4.57 (m, 1H), 5.45-5.54 (m, 1H), 5.86 (m, 2H), 6.14-6.19 (m, 1H), 6.29 (bd, 1H), 6.69-6.76 (m, 1H), 6.84 (bd, 2H), 7.22-7.45 (m, 5H). MS APCI, m/z=464 (M+Na). LC/MS 2.52 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 (1% MeOH/DCM)

Sources & evidence

ORD record
ord-39244fd5876a4891b6383aa468ab518d
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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