Dimethylformamide → HCID 178461222, compound

HRID 81278Notes

Reaction equation

HRID 81278 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[N:12][CH:11]=[CH:10][N:9]=2)[C:5]2[N:14]([CH2:29][C@H:30]3[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]3)[C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][C@H:18]3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[N:16][C:4]=2[CH:3]=1.[CH3:37][N:38](C=O)C>[C-]#N.[C-]#N.[Zn+2]>[CH3:36][C@H:33]1[CH2:34][CH2:35][C@H:30]([CH2:29][N:14]2[C:5]3[C:6]([C:8]4[CH:13]=[N:12][CH:11]=[CH:10][N:9]=4)=[N:7][C:2]([C:37]#[N:38])=[CH:3][C:4]=3[N:16]=[C:15]2[N:17]2[CH2:22][CH2:21][O:20][CH2:19][C@H:18]2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:31][CH2:32]1

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 178461218HCID 178461218, compound

Product 1

HCID 178461222HCID 178461222, compound

Reagents, catalysts & solvents 1

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

Conditions

Temperature
140 °C

Procedure

To a sealable tube were added 6-chloro-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-4-(pyrazin-2-yl)-3H-imidazo[4,5-c]pyridine (250 mg, 0.497 mmol) and Zn(CN)2 (46 mg, 0.397 mmol). DMF (4 mL) was added, and the mixture was purged with nitrogen for 5 minutes. Pd(dppf)Cl2 dichloromethane complex (20.2 mg, 0.024 mmol) was added, and the mixture was degassed with nitrogen again for 5 minutes. The tube was sealed and heated to 140° C. for 2.5 hours. The reaction mixture was cooled to room temperature, filtered, diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified on a silica gel column using 30-45% ethyl acetate/petroleum ether as eluent to afford 3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-4-(pyrazin-2-yl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCl calc'd. for C29H31N7O [M+H]+ 494. found 494.

Workup

  1. customthe mixture was purged with nitrogen for 5 minutes
  2. additionPd(dppf)Cl2 dichloromethane complex (20.2 mg, 0.024 mmol) was added
  3. customthe mixture was degassed with nitrogen again for 5 minutes
  4. customThe tube was sealed
  5. temperatureThe reaction mixture was cooled to room temperature
  6. filtrationfiltered
  7. additiondiluted with ethyl acetate
  8. washwashed with water and brine
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-c2a6a99aa69c44d5ba2c48348ee76aa3
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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