Sodium borohydride → HCID 178435874, compound

HRID 2174020Notes

Reaction equation

HRID 2174020 reaction equation
[CH2:1]([C:3]1[C:4]([CH2:19][C:20]2[NH:24][C:23]3[CH:25]=[CH:26][C:27]([C:29]#[N:30])=[CH:28][C:22]=3[N:21]=2)=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH:7]=[C:6]2[C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[CH3:2].[BH4-].[Na+]>CO.O>[CH2:1]([C:3]1[C:4]([CH2:19][C:20]2[NH:24][C:23]3[CH:25]=[CH:26][C:27]([C:29]#[N:30])=[CH:28][C:22]=3[N:21]=2)=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:13]([OH:18])[C:14]([F:17])([F:15])[F:16])[CH3:2]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 178435873HCID 178435873, compound

Product 1

HCID 178435874HCID 178435874, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 2-((5-ethyl-7-methyl-3-(2,2,2-trifluoroacetyl)-1H-indol-4-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile (60 mg, 0.114 mmol) in MeOH (10 mL) was added portionwise NaBH4 (21.6 mg, 0.572 mmol). The mixture was stirred at room temperature for 3 h, and then for 16 h at 60° C. The reaction mixture was diluted with H2O. The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic phase was washed with H2O and brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by silica gel flash column chromatography [CH2Cl2/(2M NH3 in MeOH)=94/6, isocratic] to give the title compound. 1H NMR (400 MHz, ACETONITRILE-d3 with about 5 μL TFA) δ ppm 9.50 (br. s., 1H), 7.83 (s, 1H), 7.54 (d, J=8.30 Hz, 1H), 7.47 (d, J=8.30 Hz, 1H), 7.42 (br. s., 1H), 6.95 (s, 1H), 5.56 (q, J=7.28 Hz, 1H), 4.78 (d, J=17.40 Hz, 1H), 4.64 (d, J=17.43 Hz, 1H), 2.74 (q, J=7.45 Hz, 2H), 2.45 (s, 3H), 1.12 (t, J=7.52 Hz, 3H). HRMS calcd. for C22H19F3N4O (M+H)+ 413.1584. found 413.1583.

Workup

  1. waitfor 16 h at 60° C
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with CH2Cl2
  4. washThe combined organic phase was washed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by silica gel flash column chromatography [CH2Cl2/(2M NH3 in MeOH)=94/6, isocratic]

Sources & evidence

ORD record
ord-5bb08b08ddf64d77981df11f85601858
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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