Dimethylformamide → HCID 178461223, compound

HRID 1852889Notes

Reaction equation

HRID 1852889 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH2:9][CH:10]2[CH2:13][CH2:12][CH2:11]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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH:10]1([CH2:9][O:8][C:6]2[C:5]3[N:14]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][C@H:18]4[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:16][C:4]=3[CH:3]=[C:2]([C:37]#[N:38])[N:7]=2)[CH2:13][CH2:12][CH2:11]1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 178461220HCID 178461220, compound

Product 1

HCID 178461223HCID 178461223, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
140 °C

Procedure

To a solution of 6-chloro-4-(cyclobutylmethoxy)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine (120 mg, 0.23 mmol) in DMF (1.5 mL) was added Zn(CN)2 (83 mg, 0.70 mmol), and the mixture was deoxygenated by purging with nitrogen for 10 minutes. Pd(dppf)Cl2 dichloromethane adduct (57.7 mg, 0.07 mmol) was added and the reaction was again deoxygenated for 5 minutes. The reaction flask was sealed and the mixture was heated at 140° C. for 16 h. The reaction mixture was then cooled to room temperature, diluted with EtOAc (50 mL), and the organic layer was separated. The organic layer was washed with water (2×50 mL) followed by saturated brine solution (2×30 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (40% EtOAc/petroleum ether) to yield 4-(cyclobutylmethoxy)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ES/APCI calc'd. for C30H37N5O2 [M+H]+ 500. found 500.

Workup

  1. customthe mixture was deoxygenated
  2. customby purging with nitrogen for 10 minutes
  3. customthe reaction was again deoxygenated for 5 minutes
  4. customThe reaction flask was sealed
  5. temperatureThe reaction mixture was then cooled to room temperature
  6. additiondiluted with EtOAc (50 mL)
  7. customthe organic layer was separated
  8. washThe organic layer was washed with water (2×50 mL)
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by silica gel chromatography (40% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-d883c2f4591e40bb98c7192533871e0c
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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