Ethyl Acetate → (2R)-2-(1-(5-Cyclopropyl-1H-pyrazol-3-yl)-1H-imidazo[4,5-c]pyridin-6-ylamino)-2-(4-fluorophenyl)ethanol

HRID 1092207Notes

Reaction equation

HRID 1092207 reaction equation
[NH2:1][C:2]1[C:3]([NH:19][C:20]2[CH:24]=[C:23]([CH:25]3[CH2:27][CH2:26]3)[NH:22][N:21]=2)=[CH:4][C:5]([NH:8][C@H:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:10][OH:11])=[N:6][CH:7]=1.[C:28](O)(=O)C.C(N)=N.C([O-])(O)=O.[Na+].CCOC(C)=O>CCO>[CH:25]1([C:23]2[NH:22][N:21]=[C:20]([N:19]3[C:3]4[CH:4]=[C:5]([NH:8][C@H:9]([C:12]5[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=5)[CH2:10][OH:11])[N:6]=[CH:7][C:2]=4[N:1]=[CH:28]3)[CH:24]=2)[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 160693Formamidine acetateHCID 516892Sodium BicarbonateHCID 66589154(R)-2-(5-amino-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyridin-2-ylamino)-2-(4-fluorophenyl)ethanol

Product 1

HCID 66589298(2R)-2-(1-(5-Cyclopropyl-1H-pyrazol-3-yl)-1H-imidazo[4,5-c]pyridin-6-ylamino)-2-(4-fluorophenyl)ethanolYield 153%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (R)-2-(5-amino-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyridin-2-ylamino)-2-(4-fluorophenyl)ethanol (Method 93, 0.14 g, 0.38 mmol) and formamidine acetate (0.079 g, 0.76 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=20:1) to give the title compound as an off-white solid (0.22 g, 32%). 1H NMR (400 MHz) 12.76 (s, 1H), 8.40 (s, 1H), 8.34 (s, 1H), 7.43 (m, 2H), 7.10 (m, 2H), 6.92 (s, 1H), 6.72 (d, J=7.2 Hz, 1H), 6.25 (s, 1H), 4.92 (m, 2H), 3.62 (m, 2H), 1.97 (m, 1H), 1.02 (m, 2H), 0.77 (m, 2H). MS: Calcd.: 378; Found: [M+H]+ 379.

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=20:1)

Sources & evidence

ORD record
ord-8dac3ee81c4c453ea8983258185ada04
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

Loading…