Ethyl Acetate → 3-(5-Cyclopropyl-1H-pyrazol-3-yl)-4,6-difluoro-N-((S)-1-(4-fluorophenyl)ethyl)-3H-benzo[d]imidazol-5-amine

HRID 1092212Notes

Reaction equation

HRID 1092212 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]([F:28])=[C:12]([NH:18][C@H:19]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH3:20])[C:13]([F:17])=[CH:14][C:15]=3[NH2:16])[CH:5]=2)[CH2:3][CH2:2]1.[C:29](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[C:11]([F:28])=[C:12]([NH:18][C@H:19]([C:21]5[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=5)[CH3:20])[C:13]([F:17])=[CH:14][C:15]=4[N:16]=[CH:29]3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 160693Formamidine acetateHCID 516892Sodium BicarbonateHCID 86621763(S)-N3-(5-Cyclopropyl-1H-pyrazol-3-yl)-2,6-difluoro-N1-(1-(4-fluorophenyl)ethyl)benzene-1,3,4-triamine

Product 1

HCID 665892003-(5-Cyclopropyl-1H-pyrazol-3-yl)-4,6-difluoro-N-((S)-1-(4-fluorophenyl)ethyl)-3H-benzo[d]imidazol-5-amine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(S)-N3-(5-Cyclopropyl-1H-pyrazol-3-yl)-2,6-difluoro-N1-(1-(4-fluorophenyl)ethyl)benzene-1,3,4-triamine (Method 101, 0.278 g, 0.718 mmol) and formamidine acetate (0.149 g, 1.44 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 (0.120 g, 42%). 1H NMR (400 MHz) 12.83 (s, 1H), 8.20 (s, 1H), 7.36 (m, 2H), 7.31 (d, J=11.2 Hz, 1H), 7.06 (t, J=8.8 Hz, 2H), 6.15 (s, 1H), 5.15 (d, J=10.4 Hz, 1H), 4.67 (m, 1H), 1.98 (m, 1H), 1.46 (d, J=6.8 Hz, 3H), 1.00 (m, 2H), 0.76 (m, 2H). MS: Calcd.: 397; Found: [M+H]+ 398.

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-fe9214a35ade4953a6de62f03e2bbfa6
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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