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

HRID 2240972Notes

Reaction equation

HRID 2240972 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.[CH3:27][NH:28][CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C1COCC1.C(O)(=O)C.ClCCCl>[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][N:28]([CH3:29])[CH3:27])[CH:18]=2)[N:6]=1

Participants

8

Reactant 4

HCID 674DimethylamineHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 16113437HCID 16113437, compound

Product 1

HCID 251263172-amino-5-[4-(difluoromethoxy)phenyl]-5-{3-[(dimethylamino)-methyl]phenyl}-3-methyl-3,5-dihydro-4H-imidazol-4-oneYield 43%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A small vial (10 ml) was charged with 3-[2-Amino-4-(4-difluoromethoxy-phenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-benzaldehyde (69 mg, 192 μmol) and 1,2-dichloroethane (DCE, 1 ml). To this was added a 2M solution of dimethylamine in THF (1 ml). After stirring overnight at room temperature sodium triacetoxyborohydride (58 mg, 270 μmol) was added followed by 1 drop of glacial acetic acid (˜12 mg), then after another 20 hours 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 32 mg (43%) 1H NMR (400 MHz, DMSO-d6) δ ppm 2.04 (s, 6H) 2.93 (s, 3H) 3.26 (s, 2H, partially obscured by solvent) 6.62 (br. s., 4H) 7.04-7.09 (m, 3H) 7.12 (t, J=74.18 Hz 1H) 7.18 (t, J=7.6 Hz, 1H) 7.27 (d, J=7.9 Hz, 1H) 7.35 (s, 1H) 7.40 (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-18cfe585e67d426b8e9dee7bbb92bb60
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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