HCID 178461965, compound → HCID 178463560, compound

HRID 243358Notes

Reaction equation

HRID 243358 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:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[CH:3]=1>CC(O)=O>[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][CH:27]=[CH:26][N:25]=3)[C:4]=2[CH:3]=1

Participants

3

Reactant 1

HCID 178461965HCID 178461965, compound2×

Product 1

HCID 178463560HCID 178463560, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of (S)—N-[4-fluoro-2-(pyridin-2-ylamino)phenyl]-2-(9H-purin-6-ylamino)propionamide (130 mg, 0.332 mmol) in AcOH (1 mL) was heated for 2 h at 80° C. A second portion of (S)—N-[4-fluoro-2-(pyridin-2-ylamino)phenyl]-2-(9H-purin-6-ylamino)propionamide (136 mg, 0.347 mmol) in AcOH (5 mL) was heated for 2 h at 100° C. The two crude reaction mixtures were combined and the volatiles removed in vacuo. The resulting residue was partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic layer was washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) then triturated in MeOH/diethyl ether to afford 182 as an off-white solid (66 mg, 26%). LCMS (Method K): RT 2.94 min [M+H]+ 375.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.89 (1H, br s), 8.61 (1H, br s), 8.20-7.80 (4H, m), 7.79-7.67 (2H, m), 7.52-7.43 (1H, m), 7.20-7.08 (2H, m), 5.86 (1H, br s), 1.63 (3H, d, J=6.82 Hz)

Workup

  1. customThe two crude reaction mixtures
  2. customthe volatiles removed in vacuo
  3. customThe resulting residue was partitioned between EtOAc
  4. washThe organic layer was washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)
  8. customthen triturated in MeOH/diethyl ether

Sources & evidence

ORD record
ord-6e79ed8d706d404c914d5b8a9e163f07
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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