Ethyl Acetate → (2R)-2-(3-(5-Cyclopropyl-1H-pyrazol-3-yl)-4,6-difluoro-3H-benzo[d]imidazol-5-ylamino)-2-(4-fluorophenyl)ethanol

HRID 1092213Notes

Reaction equation

HRID 1092213 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH:9][C@H:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH2:11][OH:12])=[C:4]([F:20])[C:3]=1[NH:21][C:22]1[CH:26]=[C:25]([CH:27]2[CH2:29][CH2:28]2)[NH:24][N:23]=1.[C:30](O)(=O)C.C(N)=N.C(=O)(O)[O-].[Na+].CCOC(C)=O>CCO>[CH:27]1([C:25]2[NH:24][N:23]=[C:22]([N:21]3[C:3]4[C:4]([F:20])=[C:5]([NH:9][C@H:10]([C:13]5[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=5)[CH2:11][OH:12])[C:6]([F:8])=[CH:7][C:2]=4[N:1]=[CH:30]3)[CH:26]=2)[CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 160693Formamidine acetateHCID 516892Sodium BicarbonateHCID 86621764(R)-2-(4-Amino-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,6-difluorophenylamino)-2-(4-fluorophenyl)ethanol

Product 1

HCID 66589182(2R)-2-(3-(5-Cyclopropyl-1H-pyrazol-3-yl)-4,6-difluoro-3H-benzo[d]imidazol-5-ylamino)-2-(4-fluorophenyl)ethanol

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(R)-2-(4-Amino-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,6-difluorophenylamino)-2-(4-fluorophenyl)ethanol (Method 104, 0.230 g, 0.57 mmol) and formamidine acetate (0.119 g, 1.14 mmol) in EtOH (10 ml) was heated at reflux for 1 hour. Saturated sodium bicarbonate solution (5 ml) and EtOAc (15 ml) were added. The organic layer was separated, washed with brine (3 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by chromatography (Hex-EtOAc=1:1) to give the title compound as off white solid (0.070 g, 30%). 1H NMR (400 MHz) 12.83 (s, 1H), 8.20 (s, 1H), 7.34 (m, 3H), 7.07 (t, J=8.8 Hz, 2H), 6.14 (s, 1H), 5.14 (d, J=9.6 Hz, 1H), 4.97 (t, J=5.6 Hz, 1H), 4.62 (m, 1H), 3.64-3.74 (m, 2H), 1.97 (m, 1H), 1.00 (m, 2H), 0.76 (m, 2H). MS: Calcd.: 413; Found: [M+H]+ 414.

Workup

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

Sources & evidence

ORD record
ord-4be7594dfdb14f5e9998281da16dac14
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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