Ethyl Acetate → 1-(5-Cyclopropyl-1H-pyrazol-3-yl)-6-((S)-1-(4-fluorophenyl)ethylamino)-1H-benzo[d]imidazole-4-carbonitrile

HRID 1092210Notes

Reaction equation

HRID 1092210 reaction equation
[NH2:1][C:2]1[C:9]([NH:10][C:11]2[CH:15]=[C:14]([CH:16]3[CH2:18][CH2:17]3)[NH:13][N:12]=2)=[CH:8][C:7]([NH:19][C@H:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH3:21])=[CH:6][C:3]=1[C:4]#[N:5].[C:29](O)(=O)C.C(N)=N.C(=O)(O)[O-].[Na+].CCOC(C)=O>CCO>[CH:16]1([C:14]2[NH:13][N:12]=[C:11]([N:10]3[C:9]4[CH:8]=[C:7]([NH:19][C@H:20]([C:22]5[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=5)[CH3:21])[CH:6]=[C:3]([C:4]#[N:5])[C:2]=4[N:1]=[CH:29]3)[CH:15]=2)[CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 160693Formamidine acetateHCID 516892Sodium BicarbonateHCID 66589170(S)-2-amino-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(1-(4-fluorophenyl)ethylamino)benzonitrile

Product 1

HCID 665891951-(5-Cyclopropyl-1H-pyrazol-3-yl)-6-((S)-1-(4-fluorophenyl)ethylamino)-1H-benzo[d]imidazole-4-carbonitrileYield 27.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The mixture of (S)-2-amino-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(1-(4-fluorophenyl)ethylamino)benzonitrile (Method 96, 3.95 g, 10 mmol) and formamidine acetate (2.2 g, 21 mmol) in EtOH (50 ml) was heated at reflux for 36 hours. After cooling, the reaction mixture was treated with saturated sodium bicarbonate solution (30 ml) and EtOAc (80 ml). The organic layer was separated, washed with brine (30 ml), and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by column chromatography (EtOAc) to give the title compound as an off-white solid (1.05 g, 26%). 1H NMR (400 MHz) 12.80 (s, 1H), 8.45 (s, 1H), 7.43 (m, 2H), 7.31 (d, J=2.0 Hz, 1H), 7.12 (m, 2H), 7.00 (d, J=2.0 Hz, 1H), 6.75 (d, J=6.8 Hz, 1H), 6.22 (d, J=2.0 Hz, 1H), 4.58 (m, 1H), 1.97 (m, 1H), 1.44 (d, J=6.4 Hz, 3H), 1.03 (m, 2H), 0.75 (m, 2H). MS: Calcd.: 386; Found: [M+H]+ 387.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 36 hours
  3. temperatureAfter cooling
  4. customThe organic layer was separated
  5. washwashed with brine (30 ml)
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by column chromatography (EtOAc)

Sources & evidence

ORD record
ord-9b8e03499dd646bf99227c8fcc017be8
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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