4-Methylmorpholine → HCID 10437469, compound

HRID 2267600Notes

Reaction equation

HRID 2267600 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.CCN=C=NCCCN(C)C.Cl.[F:59][C:60]1[CH:61]=[C:62]([CH2:67][C:68]([NH:70][C@@H:71]([CH2:95][OH:96])[C:72]([NH:74][C@H:75]2[C:81](=[O:82])[NH:80][C:79]3[CH:83]=[CH:84][CH:85]=[CH:86][C:78]=3[S:77][C@H:76]2[C:87]2[CH:92]=[C:91]([F:93])[CH:90]=[CH:89][C:88]=2[F:94])=[O:73])=[O:69])[CH:63]=[C:64]([F:66])[CH:65]=1>ClCCl>[F:59][C:60]1[CH:61]=[C:62]([CH2:67][C:68]([NH:70][C@@H:71]([CH2:95][OH:96])[C:72]([NH:74][C@@H:75]2[C:81](=[O:82])[NH:80][C:79]3[CH:83]=[CH:84][CH:85]=[CH:86][C:78]=3[S:77][C@@H:76]2[C:87]2[CH:92]=[C:91]([F:93])[CH:90]=[CH:89][C:88]=2[F:94])=[O:73])=[O:69])[CH:63]=[C:64]([F:66])[CH:65]=1

Participants

7

Reactant 5

HCID 79724-Methylmorpholine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 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-HCl (84 mg) and NMM (50 μL). The reaction mixture was stirred 2H 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 2H 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-95e8e129d9194e5cafd3b70c4d83be5c
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

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