Dimethylformamide → HCID 178437601, compound

HRID 81234Notes

Reaction equation

HRID 81234 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=2)[C:5]2[N:15]([CH2:27][C@H:28]3[CH2:33][CH2:32][C@H:31]([CH3:34])[CH2:30][CH2:29]3)[C:16]([CH:18]([C:20]3[C:25]([F:26])=[CH:24][CH:23]=[CH:22][N:21]=3)[CH3:19])=[N:17][C:4]=2[CH:3]=1.[CH3:35][N:36](C=O)C>[C-]#N.[Zn+2].[C-]#N>[Cl:14][C:12]1[CH:13]=[C:8]([C:6]2[C:5]3[N:15]([CH2:27][C@H:28]4[CH2:33][CH2:32][C@H:31]([CH3:34])[CH2:30][CH2:29]4)[C:16]([CH:18]([C:20]4[C:25]([F:26])=[CH:24][CH:23]=[CH:22][N:21]=4)[CH3:19])=[N:17][C:4]=3[CH:3]=[C:2]([C:35]#[N:36])[N:7]=2)[CH:9]=[N:10][CH:11]=1

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 178437600HCID 178437600, compound

Product 1

HCID 178437601HCID 178437601, compound

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
140 °C

Procedure

To a stirred solution of 6-chloro-4-(5-chloropyridin-3-yl)-2-[1-(3-fluoropyridin-2-yl)ethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (400 mg, 0.80 mmol) in DMF (16 mL) was added zinc cyanide (37.7 mg, 0.32 mmol), and the reaction was deoxygenated by purging with nitrogen for 10 minutes. 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (65.5 mg, 0.08 mmol) was added, and the reaction mixture was again deoxygenated for 5 minutes. The reaction was heated to 140° C. for 5 h under a nitrogen atmosphere. The reaction was then cooled to room temperature, diluted with water (25 mL), and extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with water (1×25 mL) and brine (1×25 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (eluting with 35% EtOAc/petroleum ether) to yield 4-(5-chloropyridin-3-yl)-2-[1-(3-fluoropyridin-2-yl)ethyl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCl calcd. for C27H26ClFN6 [M+H]+ 489. found 489.

Workup

  1. customthe reaction was deoxygenated
  2. customby purging with nitrogen for 10 minutes
  3. addition1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (65.5 mg, 0.08 mmol) was added
  4. customthe reaction mixture was again deoxygenated for 5 minutes
  5. temperatureThe reaction was then cooled to room temperature
  6. additiondiluted with water (25 mL)
  7. extractionextracted with ethyl acetate (2×25 mL)
  8. washThe combined organic extracts were washed with water (1×25 mL) and brine (1×25 mL)
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by silica gel chromatography (eluting with 35% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-72248da3c18743cda99e5b59516d8b64
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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