Cyclohexanone → HCID 178424474, compound

HRID 1477467Notes

Reaction equation

HRID 1477467 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.[Li]C(C)(C)C.[C:36]1(=[O:42])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1>C1COCC1>[CH3:24][C:21]1([CH3:25])[CH2:22][CH2:23][C:18]([C:4]2[CH:3]=[C:2]([C:36]3([OH:42])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)[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

6

Reactant 4

HCID 7967CyclohexanoneHCID 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 178424474HCID 178424474, compoundYield 45.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 4-cyano-1H-imidazole-2-carboxylic acid [4-bromo-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide (159 mg, 0.397 mmol, as prepared in Example 1, step (g)) in THF (15 mL) was placed under Ar, cooled to −78° C., and treated with i-PrMgCl (199 μL, 0.397 mmol). The mixture was warmed to RT, allowed to stir at that temperature for 10 min, cooled to −78° C., treated with t-BuLi (701 μL, 1.19 mmol), stirred at that temperature for 10 min, and then treated with cyclohexanone (411 μL, 3.97 mmol). The mixture was warmed to RT, stirred 1.5 h, quenched with satd aq NH4Cl (20 mL), and extracted with EtOAc (2×50 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Silica gel chromatography of the residue with 25-50% EtOAc-hexane on a 20-g Isolute SPE column afforded 75.0 mg (45%) of the title compound as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 12.11-11.91 (br s, 1H), 9.63 (s, 1H), 8.31 (d, 1H, J=8.4 Hz), 7.71 (s, 1H), 7.43 (dd, 1H, J=8.4, 2.0 Hz), 7.36 (d, 1H, J=2.0 Hz), 5.82-5.75 (m, 1H), 3.77-3.67 (m, 1H), 2.62-2.53 (m, 1H), 2.42-2.24 (m, 4H), 2.17-2.07 (m, 2H), 1.96-1.55 (m, 10H), 1.10 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C25H30NO2, 419.2 (M+H). found 419.1.

Workup

  1. temperatureThe mixture was warmed to RT
  2. temperaturecooled to −78° C.
  3. stirringstirred at that temperature for 10 min
  4. temperatureThe mixture was warmed to RT
  5. stirringstirred 1.5 h
  6. customquenched with satd aq NH4Cl (20 mL)
  7. extractionextracted with EtOAc (2×50 mL)
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6691d3dc90674a1fbbe1d8630bd88f04
Source dataset
uspto-grants-2016_08
Patent number
US09403804B2

Reaction notes

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