Acetone → HCID 178424524, compound

HRID 1508047Notes

Reaction equation

HRID 1508047 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][C:21]([CH3:25])([CH3:24])[CH2:20][CH:19]=2)[CH:3]=1.C([Mg]Cl)(C)C.C([Li])(C)(C)C.[CH3:36][C:37]([CH3:39])=[O:38].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[CH3:24][C:21]1([CH3:25])[CH2:22][CH2:23][C:18]([C:4]2[CH:3]=[C:2]([C:37]([OH:38])([CH3:39])[CH3:36])[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])=[CH:19][CH2:20]1

Participants

8

Reactant 5

HCID 180AcetoneHCID 25517Ammonium ChlorideHCID 178418306HCID 178418306, compoundHCID 178418918HCID 178418918, compoundHCID 1784244434-Cyano-1H-imidazole-2-carboxylic acid [4-bromo-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide

Product 1

HCID 178424524HCID 178424524, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-cyano-1H-imidazole-2-carboxylic acid [4-bromo-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide (as prepared in the previous step, 200 mg, 0.501 mmol) in 8 mL of THF at −78° C. under Ar was added isopropylmagnesium chloride (275 μL, 0.551 mmol, 2.0 M in THF). The resulting mixture was warmed to RT and stirred for 5 min, cooled to −78° C. again. To the mixture was added tert-butyllithium (884 μL, 1.50 mmol, 1.7 M in pentane) and the resulting mixture was stirred at −78° C. for 10 min. Acetone (736 μL, 10.0 mmol) was then added, and the reaction was warmed to RT and stirred for 0.5 h under Ar. The mixture was treated with 5 mL of saturated NH4Cl followed by 40 mL of EtOAc, washed with brine (10 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (1-4% MeOH/DCM) gave 101 mg (53%) of the title compound as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 12.52 (s, 1H), 9.68 (s, 1H), 8.29 (d, 1H, J=8.6 Hz), 7.72 (d, 1H, J=2.3 Hz), 7.42 (dd, 1H, J=8.6, 2.3 Hz), 7.35 (d, 1H, J=2.3 Hz), 5.78 (m, 1H), 2.64 (s, 1H, OH), 2.30 (m, 2H), 2.11 (m, 2H), 1.62 (s, 6H), 1.59 (t, 2H, J=6.5 Hz), 1.11 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C22H26N4O2, 379.2 (M+H). found 379.3.

Workup

  1. temperaturecooled to −78° C. again
  2. stirringthe resulting mixture was stirred at −78° C. for 10 min
  3. temperaturethe reaction was warmed to RT
  4. stirringstirred for 0.5 h under Ar
  5. washwashed with brine (10 mL)
  6. dry with materialdried (Na2SO4)
  7. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-ed397a8d89a54421a77c8ad644ccf5ed
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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