Dimethylformamide → HCID 15952818, compound

HRID 2263624Notes

Reaction equation

HRID 2263624 reaction equation
Cl[C:2]1[CH:28]=[CH:27][C:5]([C:6]([NH:8][CH2:9][C:10]2([CH2:23][CH:24]3[CH2:26][CH2:25]3)[CH2:15][CH2:14][CH:13]([S:16]([CH2:19][CH:20]3[CH2:22][CH2:21]3)(=[O:18])=[O:17])[CH2:12][CH2:11]2)=[O:7])=[C:4]([C:29]([F:32])([F:31])[F:30])[N:3]=1.[CH3:33][N:34](C)C=O>[C-]#N.[Zn+2].[C-]#N>[C:33]([C:2]1[CH:28]=[CH:27][C:5]([C:6]([NH:8][CH2:9][C:10]2([CH2:23][CH:24]3[CH2:26][CH2:25]3)[CH2:15][CH2:14][CH:13]([S:16]([CH2:19][CH:20]3[CH2:22][CH2:21]3)(=[O:18])=[O:17])[CH2:12][CH2:11]2)=[O:7])=[C:4]([C:29]([F:32])([F:31])[F:30])[N:3]=1)#[N:34]

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 159524216-chloro-N-({1-(cyclopropylmethyl)-4-[(cyclopropylmethyl)sulfonyl]cyclohexyl}methyl)-2-(trifluoromethyl)nicotinamide

Product 1

HCID 15952818HCID 15952818, compound

Reagents, catalysts & solvents 1

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

Conditions

Temperature
150 °C

Procedure

A mixture of 6-chloro-N-({1-(cyclopropylmethyl)-4-[(cyclopropylmethyl)sulfonyl]cyclohexyl}methyl)-2-(trifluoromethyl)nicotinamide (37 mg, 0.076 m-mol), zinc cyanide (44 mg, 0.38 mmol) and tetrakis triphenylphosphine palladium (0) (8.7 mg, 0.008 mmol) in N,N-dimethylformamide (1.5 mL) was heated at 150° C. for 600 s under microwave irradiation. The mixture was allowed to cool to ambient temperature, the supernatant layer removed and evaporated. The residue was partitioned between dichloromethane (5 ml) and water (5 ml) and stirred vigorously for 5 min. The mixture separated using a 5 micron PTFE frit and the filtrate was evaporated. The yellow oil was purified by preparative plate chromatography eluting with 10% ethyl acetate in dichloromethane. Collecting the appropriate band followed by trituration with ethyl acetate, filtration of the solid and evaporation of the filtrate gave a white solid. The solid was recrystallised from ethyl acetate/isohexane which gave 6-cyano-N-({1-(cyclopropylmethyl)-4-[(cyclopropylmethyl)sulfonyl]cyclohexyl}methyl)-2-(trifluoromethyl)-nicotinamide a white solid (21 mg, 57%): 1H NMR (400 MHz, CDCl3) δ 8.11 (1H, d, J=7.9 Hz), 7.95 (1H, d, J=7.9 Hz), 5.98 (1H, s), 3.61 (2H, d, J=6.3 Hz), 2.98-2.88 (3H, m), 2.04-2.01 (2H, m), 1.96-1.84 (4H, m), 1.43-1.37 (2H, m), 1.24 (2H, d, J=6.7 Hz), 1.18-1.12 (1H, m), 0.76 (2H, q, J=6.4 Hz), 0.68-0.64 (1H, m), 0.53-0.49 (2H, m), 0.41 (2H, q, J=5.3 Hz), 0.06-0.05 (2H, m); m/z=484 (M+H+).

Workup

  1. temperatureto cool to ambient temperature
  2. customthe supernatant layer removed
  3. customevaporated
  4. customThe residue was partitioned between dichloromethane (5 ml) and water (5 ml)
  5. customThe mixture separated
  6. customthe filtrate was evaporated
  7. customThe yellow oil was purified by preparative plate chromatography
  8. washeluting with 10% ethyl acetate in dichloromethane
  9. customCollecting the appropriate band
  10. filtrationfollowed by trituration with ethyl acetate, filtration of the solid and evaporation of the filtrate
  11. customgave a white solid
  12. customThe solid was recrystallised from ethyl acetate/isohexane which

Sources & evidence

ORD record
ord-142dd5ecb74f45a1b3fd1b6fb6d78331
Source dataset
uspto-grants-2010_12
Patent number
US07851638B2

Reaction notes

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