Acetic Acid → HCID 178463562, compound

HRID 243461Notes

Reaction equation

HRID 243461 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=O)[C@@H:10]([NH:12][C:13]2[N:21]=[CH:20][N:19]=[C:18]3[C:14]=2[N:15]=[CH:16][NH:17]3)[CH3:11])=[C:4]([NH:23][C:24]2[CH:25]=[N:26][C:27](F)=[CH:28][CH:29]=2)[CH:3]=1.CC(O)=[O:33]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[N:8]=[C:9]([CH:10]([NH:12][C:13]3[N:21]=[CH:20][N:19]=[C:18]4[C:14]=3[N:15]=[CH:16][NH:17]4)[CH3:11])[N:23]([C:24]3[CH:29]=[CH:28][C:27](=[O:33])[NH:26][CH:25]=3)[C:4]=2[CH:3]=1

Participants

3

Reactant 2

HCID 176Acetic AcidHCID 178461966HCID 178461966, compound

Product 1

HCID 178463562HCID 178463562, compoundYield 16%

Conditions

Temperature
100 °C

Procedure

A mixture of (S)—N-[4-fluoro-2-(6-fluoropyridin-3-ylamino)phenyl]-2-(9H-purin-6-ylamino)propionamide (255 mg, 0.62 mmol) in AcOH (10 mL) was heated at 100° C. for 24 h. After cooling to RT, the volatiles were removed under reduced pressure and the residue was partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The aqueous phase was extracted with EtOAc and the combined organic fractions washed with water, followed by brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-20% 2M NH3/MeOH in DCM) to afford 382 as a pink solid (38 mg, 16%). LCMS (Method K): RT 2.40 min [M+H]+ 391.0. 1H NMR (DMSO-d6+TFA-D, 400 MHz, 80° C.): δ 8.58-8.49 (2H, m), 7.82 (1H, d, J=2.96 Hz), 7.75 (1H, dd, J=8.81, 4.70 Hz), 7.51 (1H, dd, J=9.59, 2.99 Hz), 7.21-7.07 (2H, m), 6.40 (1H, d, J=9.60 Hz), 5.86 (1H, br d), 1.79 (3H, d, J=6.82 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customthe volatiles were removed under reduced pressure
  3. customthe residue was partitioned between EtOAc
  4. extractionThe aqueous phase was extracted with EtOAc
  5. washthe combined organic fractions washed with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-20% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-0fd3ae7066154f89b20d23fc3e70307b
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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