HCID 68157901, compound → HCID 68157902, compound

HRID 243173Notes

Reaction equation

HRID 243173 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][C@H:8]([C:10](=O)[NH:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)[C:13]=1[NH:25][CH2:26][CH2:27][O:28][CH3:29])[CH3:9])([CH3:4])([CH3:3])[CH3:2]>CC(O)=O>[C:1]([O:5][C:6](=[O:31])[NH:7][C@H:8]([C:10]1[N:25]([CH2:26][CH2:27][O:28][CH3:29])[C:13]2[C:14]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)=[C:15]([F:18])[CH:16]=[CH:17][C:12]=2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 1

HCID 68157901HCID 68157901, compound

Product 1

HCID 68157902HCID 68157902, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of {(S)-1-[4-fluoro-2-(2-methoxyethylamino)-3-pyridin-2-yl-phenylcarbamoyl]ethyl}carbamic acid tert-butyl ester (368 mg, 0.85 mmol) in AcOH (5 mL) was heated for 16 h at 70° C. in a sealed tube. After cooling to RT, the volatiles were removed in vacuo and the resulting residue taken up in DCM (15 mL) and washed with sat. NaHCO3 (30 mL). The aqueous was further extracted with DCM (2×15 mL). The combined organic fractions were washed with brine (15 mL), dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PPC, gradient 20-75% EtOAc/cyclohexane) to afford the title compound as a white solid (239 mg, 68%). LCMS (Method C): RT 2.92 min [M+H]+ 415. 1H NMR (CDCl3, 400 MHz): δ 7.84 (1H, ddd, J=7.5, 7.5, 2.0 Hz), 7.71 (1H, dd, J=9.0, 5.0 Hz), 7.59-7.56 (1H, m), 7.38 (1H, ddd, J=7.5, 5.0, 1.5 Hz), 7.09 (1H, dd, J=10.5, 9.0 Hz), 5.29-5.19 (2H, m), 4.33-4.26 (1H, m), 3.91 (1H, ddd, J=15.0, 4.0, 4.0 Hz), 3.14-3.08 (2H, m), 3.07 (1H, s), 1.60 (3H, d, J=6.5 Hz), 1.41 (9H, s)

Workup

  1. customthe volatiles were removed in vacuo
  2. washwashed with sat. NaHCO3 (30 mL)
  3. extractionThe aqueous was further extracted with DCM (2×15 mL)
  4. washThe combined organic fractions were washed with brine (15 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PPC, gradient 20-75% EtOAc/cyclohexane)

Sources & evidence

ORD record
ord-2e2e855cfa33459a8b49dcdd7541696a
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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