4-Methylmorpholine → HCID 10369746, compound

HRID 2267595Notes

Reaction equation

HRID 2267595 reaction equation
FC1C=C(CC(N[C@H](C(O)=O)C)=O)C=C(F)C=1.CCN=C=NCCCN(C)C.Cl.CN1CCOCC1.[F:37][C:38]1[CH:39]=[C:40]([CH2:45][C:46]([NH:48][C@H:49]([C:51]([NH:53][C@H:54]2[C:60](=[O:61])[NH:59][C:58]3[CH:62]=[CH:63][CH:64]=[CH:65][C:57]=3[S:56][C@H:55]2[C:66]2[CH:71]=[C:70]([F:72])[CH:69]=[CH:68][C:67]=2[F:73])=[O:52])[CH3:50])=[O:47])[CH:41]=[C:42]([F:44])[CH:43]=1>ClCCl>[F:37][C:38]1[CH:39]=[C:40]([CH2:45][C:46]([NH:48][C@H:49]([C:51]([NH:53][C@@H:54]2[C:60](=[O:61])[NH:59][C:58]3[CH:62]=[CH:63][CH:64]=[CH:65][C:57]=3[S:56][C@@H:55]2[C:66]2[CH:71]=[C:70]([F:72])[CH:69]=[CH:68][C:67]=2[F:73])=[O:52])[CH3:50])=[O:47])[CH:41]=[C:42]([F:44])[CH:43]=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 68605834HCID 68605834, compound

Product 1

HCID 10369746HCID 10369746, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of racemic 2,3-cis-3-amino-2-(2,5-difluorophenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (1d) (300 mg) in dichloromethane (40 mL) at 0° C. under nitrogen was added N-[(3,5-difluorophenyl)acetyl]-L-alanine (1e) (238 mg), HOBt-hydrate (330 mg), EDAC-HCl (282 mg) and NMM (165 mg). The reaction mixture was stirred 1 h at 0° C., concentrated in vacuo and partitioned between water (100 mL) and ethyl acetate (125 mL). The organic phase was collected and consecutively washed with water, saturated aqueous sodium bicarbonate, and brine, dried, filtered and evaporated to yield a mixture of the title compound and N2-[(3,5-difluorophenyl)acetyl]-N1-[(2S,3S)-2-(2,5-difluorophenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl]-L-alaninamide. The crude product (500 mg) was purified by flash chromatography (50% ethyl acetate/hexanes) to afford the title compound (180 mg, 69%) as an off-white solid. 1H NMR (300 MHz, CDCl3) δ1.22 (d, 3H), 3.48 (s, 2H), 4.29 (m, 1H), 4.93 (t, 1H), 5.68 (d, 1H), 6.01 (d, 1H), 6.50 (d, 1H), 6.73-6.80 (m, 3H), 6.93-7.02 (m, 2H), 7.15 (d, 1H), 7.30 (t, 1H), 7.43 (t, 1H), 7.5-7.6 (m, 1H), 7.73 (d, 1H), 7.74 (s, 1H). MS APCI, m/z=532 (M+1). LC/MS: 2.53 min.

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between water (100 mL) and ethyl acetate (125 mL)
  3. customThe organic phase was collected
  4. washconsecutively washed with water, saturated aqueous sodium bicarbonate, and brine
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customto yield

Sources & evidence

ORD record
ord-11167cede5bb4ef1963e066c450f1fca
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

Loading…