HCID 66589124, compound → HCID 66589263, compound

HRID 1092208Notes

Reaction equation

HRID 1092208 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([N:9]3[C:13]4[CH:14]=[C:15]([NH:20][C@H:21]([C:23]5[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=5)[CH3:22])[C:16]([C:18]#[N:19])=[CH:17][C:12]=4[N:11]=[CH:10]3)[CH:5]=2)[CH2:3][CH2:2]1.[H][H]>[Pd].CO.Cl>[NH2:19][CH2:18][C:16]1[C:15]([NH:20][C@H:21]([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH3:22])=[CH:14][C:13]2[N:9]([C:6]3[CH:5]=[C:4]([CH:1]4[CH2:3][CH2:2]4)[NH:8][N:7]=3)[CH:10]=[N:11][C:12]=2[CH:17]=1

Participants

6

Reactant 2

HCID 66589124HCID 66589124, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 66589263HCID 66589263, compoundYield 64.8%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To 1-(5-cyclopropyl-1H-pyrazol-3-yl)-6-((S)-1-(4-fluorophenyl)ethylamino)-1H-benzo[d]imidazol-5-carbonitrile (Example 33, 1.25 g, 3.2 mmol) and 10% palladium on carbon (0.69 g, 0.65 mmol) in MeOH (40 ml) was added 15 drops of conc. HCl. The reaction was charged 45 psi hydrogen and shook for 30 hours. The solvent was removed. The residue was dissolved in EtOAc (200 ml), washed with saturated sodium bicarbonate (50 ml) and dried over sodium sulfate. After removal of solvent, the residue was purified by reverse-phase column chromatography (5-50% CH3CN in H2O) to give the title compound as an off-white solid (0.81 g, 61%). 1H NMR (400 MHz) 12.65 (s, 1H), 8.15 (s, 1H), 7.46 (m, 2H), 7.36 (s, 1H), 7.11 (m, 2H), 6.91 (d, J=5.6 Hz, 1H), 6.74 (s, 1H), 5.94 (s, 1H), 4.54 (m, 1H), 3.92 (s, 2H), 2.07-1.91 (m, 3H), 1.48 (d, J=6.4 Hz, 3H), 1.01 (m, 2H), 0.72 (m, 2H). MS: Calcd.: 390; Found: [M+H]+ 391.

Workup

  1. customThe solvent was removed
  2. dissolutionThe residue was dissolved in EtOAc (200 ml)
  3. washwashed with saturated sodium bicarbonate (50 ml)
  4. dry with materialdried over sodium sulfate
  5. customAfter removal of solvent
  6. customthe residue was purified by reverse-phase column chromatography (5-50% CH3CN in H2O)

Sources & evidence

ORD record
ord-7145ca59675a4683ac2452f3d586623b
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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