Sodium cyanoborohydride → HCID 57666422, compound

HRID 1907949Notes

Reaction equation

HRID 1907949 reaction equation
C([BH3-])#N.[Na+].[NH2:5][C:6]1[C:11]2[N:12]=[C:13]([CH2:28][O:29][N:30]=[C:31]([CH3:33])[CH3:32])[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:10]=2[C:9]([CH3:34])=[C:8]([CH3:35])[N:7]=1.C(O)(=O)C.CO>O1CCCC1>[NH2:5][C:6]1[C:11]2[N:12]=[C:13]([CH2:28][O:29][NH:30][CH:31]([CH3:32])[CH3:33])[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:10]=2[C:9]([CH3:34])=[C:8]([CH3:35])[N:7]=1

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 10129899Acetic acid methanolHCID 57576721HCID 57576721, compound

Product 1

HCID 57666422HCID 57666422, compoundYield 30.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of sodium cyanoborohydride in tetrahydrofuran (1 M, 6 mL) was added to a solution of N-{4-[4-amino-6,7-dimethyl-2-({[(1-methylethylidene)amino]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]butyl}benzamide (260 mg, 0.62 mmol) in 1:2 acetic acid/methanol (9 mL). The reaction mixture was stirred overnight, concentrated under reduced pressure, and partitioned between 1 M aqueous hydrochloric acid (20 mL) and chloroform (5 mL). After the bubbling subsided, the layers were separated and the aqueous phase was washed with chloroform (2×5 mL). The organic layers were combined and back-extracted with 1 M aqueous hydrochloric acid (2×5 mL). The aqueous layers were combined and adjusted to pH 10 with 1 M aqueous sodium hydroxide, then were extracted with chloroform (4×). The organic layers were combined, washed with saturated aqueous sodium bicarbonate (5 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to yield a foam. The foam was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 3-35% CMA in chloroform) followed by crystallization from acetonitrile. The crystals were isolated by filtration and dried under vacuum at 70° C. to yield 80 mg of N-[4-(4-amino-2-{[(isopropylamino)oxy]methyl}-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)butyl]benzamide as a white powder, mp 161.0-162.0° C.

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompartitioned between 1 M aqueous hydrochloric acid (20 mL) and chloroform (5 mL)
  3. customthe layers were separated
  4. washthe aqueous phase was washed with chloroform (2×5 mL)
  5. extractionback-extracted with 1 M aqueous hydrochloric acid (2×5 mL)
  6. extractionwere extracted with chloroform (4×)
  7. washwashed with saturated aqueous sodium bicarbonate (5 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto yield a foam
  12. customThe foam was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 3-35% CMA in chloroform)
  13. customfollowed by crystallization from acetonitrile
  14. customThe crystals were isolated by filtration
  15. customdried under vacuum at 70° C.

Sources & evidence

ORD record
ord-06b4e7277893426f8e8f6546894d9eaa
Source dataset
uspto-grants-2013_12
Patent number
US08598192B2

Reaction notes

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