4-Methylmorpholine → HCID 10437469, compound

HRID 1593268Notes

Reaction equation

HRID 1593268 reaction equation
FC1C=C(CC(N[C@H](C(O)=O)CO)=O)C=C(F)C=1.N[C@H]1C(=O)NC2C=CC=CC=2S[C@H]1C1C=C(F)C=CC=1F.CN1CCOCC1.[F:47][C:48]1[CH:49]=[C:50]([CH2:55][C:56]([NH:58][C@@H:59]([CH2:83][OH:84])[C:60]([NH:62][C@H:63]2[C:69](=[O:70])[NH:68][C:67]3[CH:71]=[CH:72][CH:73]=[CH:74][C:66]=3[S:65][C@H:64]2[C:75]2[CH:80]=[C:79]([F:81])[CH:78]=[CH:77][C:76]=2[F:82])=[O:61])=[O:57])[CH:51]=[C:52]([F:54])[CH:53]=1>ClCCl>[F:47][C:48]1[CH:49]=[C:50]([CH2:55][C:56]([NH:58][C@@H:59]([CH2:83][OH:84])[C:60]([NH:62][C@@H:63]2[C:69](=[O:70])[NH:68][C:67]3[CH:71]=[CH:72][CH:73]=[CH:74][C:66]=3[S:65][C@@H:64]2[C:75]2[CH:80]=[C:79]([F:81])[CH:78]=[CH:77][C:76]=2[F:82])=[O:61])=[O:57])[CH:51]=[C:52]([F:54])[CH:53]=1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 68605074HCID 68605074, compoundHCID 68605157HCID 68605157, compoundHCID 68606664HCID 68606664, compound

Product 1

HCID 10437469HCID 10437469, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution N-[(3,5-difluorophenyl)acetyl]-L-serine (4b (75 mg) in dichloromethane (15 mL) at 0° C. under N2, was added racemic 2,3-cis-3-amino-2-(2,5-difluorophenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one-HCl (1d) (100 mg) followed by the HOBt-hydrate (97 mg) and NMM (32 μL). Reaction stirred for 5 min. and then added EDAC-HC1 (84 mg) and NMM (50 μL). The reaction mixture was stirred 2 H at 0° C. under N2, 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, brine, dried, filtered and evaporated to yield a mixture of the title compound and (2S)-2-{[(3,5-difluorophenyl)acetyl]amino}-N-[(2S,3S)-2-(2,5-difluorophenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl]-3-hydroxypropanamide. The crude product (165 mg) was purified by flash chromatography (80% ethyl acetate/hexanes) to afford the title compound (60 mg, 73%) as a white solid. 1H NMR (300 MHz, d6-DMSO) δ(d, 3H), 3.48 (s, 2H), 4.21 (q, 1H), 4.74, (t, 1H), 4.85 (bs, 1H), 5.50 (d, 1H), 6.93 (d, 2H), 7.09 (m, 1H), 7.18-7.35 (m, 4H), 7.45-7.55 (m, 2H), 7.71 (t, 2H), 8.17(d, 1H), 10.68 (s, 1H). MS APCI, m/z=548 (M+1). LC/MS: 2.34 min.

Workup

  1. customReaction
  2. stirringThe reaction mixture was stirred 2 H at 0° C. under N2
  3. concentrationconcentrated in vacuo
  4. custompartitioned between water (100 mL) and ethyl acetate (125 mL)
  5. customThe organic phase was collected
  6. washconsecutively washed with water, saturated aqueous sodium bicarbonate, brine
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customto yield

Sources & evidence

ORD record
ord-54b6abb2cb9e48f2bbd83346e47f40da
Source dataset
uspto-grants-2007_11
Patent number
US07294622B2

Reaction notes

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