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

HRID 1092205Notes

Reaction equation

HRID 1092205 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[CH:11]=[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:28](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: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:28]3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 160693Formamidine acetateHCID 516892Sodium BicarbonateHCID 67478890HCID 67478890, compound

Product 1

HCID 665891053-(5-Cyclopropyl-1H-pyrazol-3-yl)-6-fluoro-N-[(S)-1-(4-fluorophenyl)ethyl]-3H-benzo[d]imidazol-5-amineYield 55%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of (S)-N3-(5-cyclopropyl-1H-pyrazol-3-yl)-6-fluoro-N1-[1-(4-fluorophenyl)ethyl]benzene-1,3,4-triamine (Method 73; 0.302 g, 0.816 mmol) and formamidine acetate (0.170 g, 1.63 mmol) in EtOH (10 ml) was heated at reflux for 1 hr. After cooling, the reaction mixture was treated with saturated sodium bicarbonate solution (5 ml) and EtOAc (15 ml). The organic layer was separated, washed with brine (3 ml), and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane:EtOAc=1:1) to give the title compound as an off-white solid (0.170 g, 55%). NMR (400 MHz) 12.69 (s, 1H), 8.27 (s, 1H), 7.47 (m, 2H), 7.39 (d, J=12.0 Hz, 1H), 7.12 (t, J=9.0 Hz, 2H), 6.96 (d, J=8.0 Hz, 1H), 6.07 (s, 1H), 5.90 (d, J=4.8 Hz, 1H), 4.56 (m, 1H), 1.96 (m, 1H), 1.51 (d, J=6.8 Hz, 3H), 1.02 (m, 2H), 0.76 (m, 2H). MS: Calcd.: 379; Found: [M+H]+ 380.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 hr
  3. temperatureAfter cooling
  4. customThe organic layer was separated
  5. washwashed with brine (3 ml)
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by column chromatography (hexane:EtOAc=1:1)

Sources & evidence

ORD record
ord-647f56f32907420c87c4866b36f753bc
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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