Ethylamine → 2-amino-5-[4-(difluoromethoxy)phenyl]-5-{3-[(ethylamino)-methyl]phenyl}-3-methyl-3,5-dihydro-4H-imidazol-4-one

HRID 2240973Notes

Reaction equation

HRID 2240973 reaction equation
[NH2:1][C:2]1[N:3]([CH3:26])[C:4](=[O:25])[C:5]([C:17]2[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=2)[CH:20]=O)([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH:14]([F:16])[F:15])=[CH:9][CH:8]=2)[N:6]=1.[CH2:27]([NH2:29])[CH3:28].[BH4-].[Na+].[OH-].[Na+]>C1COCC1.CO>[NH2:1][C:2]1[N:3]([CH3:26])[C:4](=[O:25])[C:5]([C:7]2[CH:8]=[CH:9][C:10]([O:13][CH:14]([F:15])[F:16])=[CH:11][CH:12]=2)([C:17]2[CH:24]=[CH:23][CH:22]=[C:19]([CH2:20][NH:29][CH2:27][CH3:28])[CH:18]=2)[N:6]=1

Participants

7

Reactant 4

HCID 6341EthylamineHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 16113437HCID 16113437, compound

Product 1

HCID 251263162-amino-5-[4-(difluoromethoxy)phenyl]-5-{3-[(ethylamino)-methyl]phenyl}-3-methyl-3,5-dihydro-4H-imidazol-4-oneYield 83%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A small vial (2 ml) was charged with 3-[2-Amino-4-(4-difluoromethoxy-phenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-benzaldehyde (68 mg, 189 μmol) and THF (0.5 ml). To this was added a 2M solution of ethylamine in THF (100 μl). After stirring overnight methanol (1 ml) and sodium borohydride (11 mg) was added, then after another hour 1N sodium hydroxide (1 ml) was added and the mixture extracted with diethyl ether. The ethereal layer was concentrated by rotary evaporation, diluted with methanol and re-concentrated (repeated three times). Finally the oily residue was redissolved in diethylether/hexanes and concentrated, twice then placed under vacuum to give a white foam 61 mg (83%). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.95 (t, J=7.1 Hz, 3H) 2.38-2.44 (m, 2H, partially obscured by solvent) 2.93 (s, 3H) 3.56 (s, 2H) 6.61 (br. s., 2H) 6.66 (br. s., 1H) 7.05 (d, J=8.8 Hz, 2H) 7.12 (t, J=74.18 Hz, 1H) 7.14-7.28 (m, 3H) 7.33-7.39 (m, 1H) 7.42 (d, J=8.8 Hz, 2H); MS (APPI) m/z 389 [M+H]+

Workup

  1. additionwas added
  2. extractionthe mixture extracted with diethyl ether
  3. concentrationThe ethereal layer was concentrated by rotary evaporation
  4. additiondiluted with methanol
  5. concentrationre-concentrated (repeated three times)
  6. dissolutionFinally the oily residue was redissolved in diethylether/hexanes
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-866a930274fc4ff8ab7e2ed04d59070b
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

Loading…