Methanol → 1-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea

HRID 1505159Notes

Reaction equation

HRID 1505159 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH2:10])=[C:5]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:4]=1.ClC(Cl)(O[C:23](=[O:29])OC(Cl)(Cl)Cl)Cl.[N-:31]=[C:32]=O.CO.[CH3:36][N:37]([CH:39]=[O:40])C>CCOC(C)=O>[F:18][C:2]([F:1])([F:17])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH:10][C:39]([NH:37][C:36]2[C:32]3[NH:31][C:23](=[O:29])[NH:10][C:9]=3[CH:6]=[CH:5][CH:4]=2)=[O:40])=[C:5]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:4]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 94429TriphosgeneHCID 105034IsocyanateHCID 58873623(4-(Trifluoromethyl)-2-(piperidin-1-yl)phenyl)-methanamine

Product 1

HCID 534773871-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)ureaYield 18%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

Amine 2c (500 mg, 1.9 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (580 mg, 2 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1a (265 mg, 1.78 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 9.5/MeOH 0.5). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 140 mg of a pale yellow solid. Yield=18% 1HNMR (DMSO, 400 MHz) δ 1.54 (2H, m), 1.68 (4H, m), 2.85 (4H, m), 4.42 (2H, d, J=6 Hz), 6.63 (1H, d, J=7.6 Hz), 6.76 (1H, t), 6.84 (1H, t, J=8.4 Hz), 6.95 (1H, d, J=8.4 Hz), 7.31 (1H, s), 7.41 (1H, d), 7.52 (1H, d, J=8.4 Hz), 8.33 (1H, s), 10.01 (1H, bs), 10.60 (1H, bs); [M+1] 434.11 (C21H22F3N5O2 requires 433.43).

Workup

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutionthe residue was dissolved in 5 ml of DMF
  4. temperaturethe mixture was warmed at 80° C. for 8 hours
  5. customThe solvent was evaporated
  6. dissolutionthe crude was dissolved in AcOEt (30 ml)
  7. washwashed with water (1×20 ml) and brine
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated under vacuum
  10. customThe purification of the crude residue by chromatographic column

Sources & evidence

ORD record
ord-8472556acb5a42018cd4f910403f2ecd
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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