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

HRID 1505166Notes

Reaction equation

HRID 1505166 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][NH2:13])=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.ClC(Cl)(O[C:18](=[O:24])OC(Cl)(Cl)Cl)Cl.[N-:26]=[C:27]=O.[CH3:29][OH:30]>CCOC(C)=O.CN(C=O)C>[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][NH:13][C:29]([NH:1][C:6]3[C:27]4[NH:26][C:18](=[O:24])[NH:13][C:12]=4[CH:9]=[CH:8][CH:7]=3)=[O:30])=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 887MethanolHCID 94429TriphosgeneHCID 105034IsocyanateHCID 70178344-(Pyrrolidin-1-yl)benzylamine

Product 1

HCID 534758071-(4-(pyrrolidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)ureaYield 16%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

(4-(pyrrolidin-1-yl)phenyl)methanamine 2l (774 mg, 4.4 mmol) was dissolved in 40 ml of AcOEt and at 0° C. triphosgene (1.3 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 (660 mg, 4.4 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 (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 250 mg of a white solid. Yield=16% 1HNMR (DMSO, 200 MHz) δ 1.92 (4H, m), 3.17 (4H, m), 4.17 (2H, d, J=5.6 Hz), 6.58 (4H, m), 6.84 (2H, m), 7.12 (2H, d, J=8.6 Hz), 8.16 (1H, bs), 9.93 (1H, bs), 10.58 (1H, bs); [M+1] 352.3 (C19H21N5O2 requires 351.4).

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-b7b600fedaeb494b842f3d9057d6c32f
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Reaction notes

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