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

HRID 1505169Notes

Reaction equation

HRID 1505169 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][NH2:14])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.ClC(Cl)(O[C:19](=[O:25])OC(Cl)(Cl)Cl)Cl.[N-:27]=[C:28]=O.[CH3:30][N:31]([CH:33]=[O:34])C>CCOC(C)=O>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][NH:14][C:33]([NH:31][C:30]3[C:28]4[NH:27][C:19](=[O:25])[NH:1][C:2]=4[CH:3]=[CH:4][CH:5]=3)=[O:34])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 94429TriphosgeneHCID 105034IsocyanateHCID 2795551(4-Piperidinophenyl)methylamine

Product 1

HCID 534758081-(4-(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

(4-(piperidin-1-yl)phenyl)methanamine 2m (1.47 g, 7.8 mmol) was dissolved in 40 ml of AcOEt and at 0° C. triphosgene (2.3 g, 1 equiv.) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 20 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1a (1.15 g, 7.8 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt). The solvent was evaporated and the crude was dissolved in AcOEt (50 ml) and washed with water (1×30 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 520 mg of a pale yellow solid. Yield=18% 1HNMR (DMSO, 200 MHz) δ 1.58 (6H, m), 3.08 (4H, m), 4.19 (2H, d, J=6 Hz), 6.62 (2H, m), 6.86 (4H, m), 7.15 (2H, d, J=8.8 Hz), 8.19 (1H, bs), 9.95 (1H, bs), 10.58 (1H, bs); [M+1] 366.3 (C20H23N5O2 requires 365.43).

Workup

  1. additionwas added to the solution
  2. customthen evaporated
  3. dissolutionthe residue was dissolved in 20 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 (50 ml)
  7. washwashed with water (1×30 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-c310cb245c29467391c1ff1c6f57c815
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

Loading…