Acetone → HCID 178458516, compound

HRID 1190083Notes

Reaction equation

HRID 1190083 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[C:4]([C:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]=2)[CH:3]=1.C([Mg]Cl)(C)C.C([Li])(C)(C)C.[CH3:34][C:35]([CH3:37])=[O:36].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[C:18]1([C:4]2[CH:3]=[C:2]([C:35]([OH:36])([CH3:37])[CH3:34])[CH:7]=[CH:6][C:5]=2[NH:8][C:9]([C:11]2[NH:12][CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]=1

Participants

8

Reactant 5

HCID 180AcetoneHCID 25517Ammonium ChlorideHCID 178418306HCID 178418306, compoundHCID 178418918HCID 178418918, compoundHCID 178510376HCID 178510376, compound

Product 1

HCID 178458516HCID 178458516, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-cyano-1H-imidazole-2-carboxylic acid (4-bromo-2-cyclohex-1-enyl-phenyl)-amide (as prepared in the previous step, 50.0 mg, 0.135 mmol) in 2 mL of THF at −78° C. under Ar was added isopropyl magnesium chloride (71 μL, 0.14 mmol, 2.0 M in THF). The resulting mixture was warmed to RT and stirred for 15 min, cooled to −78° C. again. To the mixture was added tert-butyllithium (240 μL, 0.405 mmol, 1.7 M in pentane) and the resulting mixture was stirred at −78° C. for 5 min and then acetone (0.40 mL, 0.68 mmol) was added. The reaction was warmed to RT and stirred for 1 h under Ar. The mixture was treated with 1 mL of saturated NH4Cl followed by 40 mL of EtOAc and washed with H2O (10 mL), brine (5 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (1-2% MeOH/DCM) gave 32.1 mg (68%) of the title compound as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 11.88 (s, 1H), 9.58 (s, 1H), 8.29 (d, 1H, J=8.6 Hz), 7.74 (s, 1H), 7.42 (dd, 1H, J=8.6, 2.2 Hz), 7.35 (d, 1H, J=2.2 Hz), 5.87 (m, 1H), 2.23-2.34 (m, 4H), 1.73-1.90 (m, 4H), 1.79 (s, 1H, OH), 1.61 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C20H22N4O2, 351.2 (M+H). found 351.0.

Workup

  1. temperaturecooled to −78° C. again
  2. stirringthe resulting mixture was stirred at −78° C. for 5 min
  3. temperatureThe reaction was warmed to RT
  4. stirringstirred for 1 h under Ar
  5. washwashed with H2O (10 mL), brine (5 mL)
  6. dry with materialdried (Na2SO4)
  7. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-5affbf2bc0ab4bad9addb14e50701020
Source dataset
uspto-grants-2014_03
Patent number
US08674100B2

Reaction notes

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