Water → HCID 68681210, compound

HRID 2263610Notes

Reaction equation

HRID 2263610 reaction equation
Cl[C:2]1[N:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:3]=1[C:4]([NH:6][CH2:7][C:8]1([CH2:21][CH:22]2[CH2:24][CH2:23]2)[CH2:13][CH2:12][CH:11]([S:14]([CH2:17][CH:18]2[CH2:20][CH2:19]2)(=[O:16])=[O:15])[CH2:10][CH2:9]1)=[O:5].[CH3:33][S-:34].[Na+].O>CC(O)C>[CH:18]1([CH2:17][S:14]([CH:11]2[CH2:12][CH2:13][C:8]([CH2:7][NH:6][C:4](=[O:5])[C:3]3[CH:25]=[CH:26][C:27]([C:29]([F:32])([F:31])[F:30])=[N:28][C:2]=3[S:34][CH3:33])([CH2:21][CH:22]3[CH2:24][CH2:23]3)[CH2:9][CH2:10]2)(=[O:16])=[O:15])[CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 962WaterHCID 4378561Sodium methanethiolateHCID 86609534HCID 86609534, compound

Product 1

HCID 68681210HCID 68681210, compoundYield 97.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 2-chloro-N-(4-cyclopropylmethanesulfonyl-1-cyclopropylmethylcyclohexylmethyl)-6-trifluoromethylnicotinamide (75 mg, 0.15 mmol) in propan-2-ol (5 ml) was treated with sodium thiomethoxide (21 mg, 0.30 mmol) and the mixture was heated under reflux for 4 hours. Water (1 ml) was added and the solvent was evaporated. The residue was partitioned between dichloromethane (5 ml) and water (5 ml) and the layers were separated using a 5 micron PTFE frit and the filtrate was evaporated. The residue was purified by preparative plate chromatography eluting with 10% ethyl acetate in dichloromethane. Collecting the appropriate band followed by trituration of the silica with ethyl acetate, filtration and evaporation gave a pale yellow foam (74 mg, 97%). 1H NMR δ (ppm) (CDCl3): 8.00 (1H, d, J=7.8 Hz), 7.41 (1H, d, J=7.8 Hz), 6.40 (1H, s), 3.64 (2H, d, J=6.3 Hz), 2.98-2.89 (3H, m), 2.63 (3H, s), 2.09-1.90 (6H, m), 1.46-1.16 (5H, m), 0.79-0.69 (3H, m), 0.55-0.51 (2H, m), 0.45-0.40 (2H, m), 0.09-0.06 (2H, m). MS (m/e)=505.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 hours
  3. customthe solvent was evaporated
  4. customThe residue was partitioned between dichloromethane (5 ml) and water (5 ml)
  5. customthe layers were separated
  6. customthe filtrate was evaporated
  7. customThe residue was purified by preparative plate chromatography
  8. washeluting with 10% ethyl acetate in dichloromethane
  9. customCollecting the appropriate band
  10. filtrationfollowed by trituration of the silica with ethyl acetate, filtration and evaporation

Sources & evidence

ORD record
ord-198720c2f8624961a88af459dfaaabf9
Source dataset
uspto-grants-2010_12
Patent number
US07851638B2

Reaction notes

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