Ethyl Acetate → 1-(5-Cyclopropyl-1H-pyrazol-3-yl)-N-((S)-1-(4-fluorophenyl)ethyl)-1H-imidazo[4,5-c]pyridin-6-amine

HRID 1092206Notes

Reaction equation

HRID 1092206 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([NH2:16])=[CH:14][N:13]=[C:12]([NH:17][C@H:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH3:19])[CH:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[C:27](O)(=O)C.C(N)=N.C([O-])(O)=O.[Na+].CCOC(C)=O>CCO>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([N:9]3[C:10]4[CH:11]=[C:12]([NH:17][C@H:18]([C:20]5[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=5)[CH3:19])[N:13]=[CH:14][C:15]=4[N:16]=[CH:27]3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 160693Formamidine acetateHCID 516892Sodium BicarbonateHCID 67478872(S)-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N-(1-(4-fluorophenyl)ethyl)pyridine-2,4,5-triamine

Product 1

HCID 665892871-(5-Cyclopropyl-1H-pyrazol-3-yl)-N-((S)-1-(4-fluorophenyl)ethyl)-1H-imidazo[4,5-c]pyridin-6-amineYield 60%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (S)-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,4,5-triamine (Method 88, 0.15 g, 0.43 mmol) and formamidine acetate (0.089 g, 0.85 mmol) in EtOH (5 ml) was heated at reflux for 2 hours. After cooling to 25° C., the reaction mixture was treated with saturated NaHCO3 solution (10 ml) and EtOAc (30 ml). The organic layer was separated, washed with brine (10 ml), and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by column chromatography (EtOAc-MeOH=40:1) to give the title compound as an off-white solid (0.092 g, 60%). 1H NMR (400 MHz) 12.75 (s, 1H), 8.39 (s, 1H), 8.33 (s, 1H), 7.42 (m, 2H), 7.08 (m, 2H), 6.90 (s, 1H), 6.89 (d, J=2.8 Hz, 1H), 6.26 (d, J=1.6 Hz, 1H), 5.00 (m, 1H), 1.96 (m, 1H), 1.42 (d, J=6.8 Hz, 3H), 1.02 (m, 2H), 0.76 (m, 2H). MS: Calcd.: 362; Found: [M+H]+ 363.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. customThe organic layer was separated
  4. washwashed with brine (10 ml)
  5. dry with materialdried over sodium sulfate
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by column chromatography (EtOAc-MeOH=40:1)

Sources & evidence

ORD record
ord-d6c1167bff734ce096e6e2505a16f438
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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