Water → HCID 15294914, compound

HRID 22303Notes

Reaction equation

HRID 22303 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1([C:25]([F:28])([F:27])[F:26])[CH:7]([NH:8][C:9](=[O:17])[C:10]2[CH:15]=[CH:14][C:13](F)=[CH:12][CH:11]=2)[NH:6][C:5]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[N:4]1.[C:31](=O)([O-])[O-].[K+].[K+].[NH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.O>CS(C)=O>[F:29][C:2]([F:30])([F:1])[C:3]1([C:25]([F:27])([F:28])[F:26])[CH:7]([NH:8][C:9](=[O:17])[C:10]2[CH:15]=[CH:14][C:13]([N:37]3[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]3)=[CH:12][CH:11]=2)[N:6]([CH3:31])[C:5]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[N:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 8082PiperidineHCID 11430Potassium CarbonateHCID 178522536HCID 178522536, compound

Product 1

HCID 15294914HCID 15294914, compoundYield 15.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of N-[4,4-bis(trifluoromethyl)-2-(4-fluorophenyl)-4,5-dihydro-1H-imidazol-5-yl]-4-fluorobenzamide (0.9 g, 2 mmole) in dimethyl sulfoxide (5 mL) was added potassium carbonate (0.83 g, 3 equiv.) and piperidine (0.51 g, 3 equiv.). The reaction mixture was heated at 145° overnight under nitrogen. The solution was cooled to room temperature, poured into water and extracted with dichloromethane. The organic layer was washed with water and saturated sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under vacuum. The residue was purified by MPLC with 9:1 hexane-ethyl acetate to give two products. N-[4,4-bis(trifluoromethyl)-2-(4-fluorophenyl)-4,5-dihydro-1-methyl-1H-imidazol-5-yl]-4-(1-piperidinyl) benzamide (160 mg, 15%) was isolated as a white solid: mp 128°-129° ; MS m/e 517 (M+ +H); 1H NMR (CDCl3 /TMS) δ 1.67(m,6H,(CH2)3), 2.93(s,3H,NCH2), 3.33(m,4H,CH2NCH2), 6.43-6.60(m,2H,NH,CH), 6.90)d,2H,J=7, Harom), 7.13-7.20(m,2H,Harom), 7.60-7.73(m,2H,Harom). N-[4,4-bis(trifluoromethyl)-4,5-dihydro-1-methyl-2-[4-(1-piperidinyl)phenyl]-1H-imidazol-5-yl]-4-fluorobenzamide (80 mg, 8%) was isolated as a white solid: mp 123°-124°; MS m/e 517 (M+ +H); 1H NMR (CDCl3 /TMS ( δ 1.67(m,6H,(CH2)3), 3.00(s,3H,NCH3), 3.30(m,4H,CH2NCH2), 6.37(d,1H,CH), 6.60(m,2H,NH), 6.90(d,2H,J=7,Harom), 7.13-7.22(m,2H,Harom), 7.53(d,2H,J=7,Harom), 7.80-7.90(m,2H,Harom).

Workup

  1. temperatureThe reaction mixture was heated at 145° overnight under nitrogen
  2. extractionextracted with dichloromethane
  3. washThe organic layer was washed with water and saturated sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by MPLC with 9:1 hexane-ethyl acetate
  7. customto give two products

Sources & evidence

ORD record
ord-5ffacda46ffc433ea2bb88e0d237b4ef
Source dataset
uspto-grants-1995_06
Patent number
US05428041

Reaction notes

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