Toluene → HCID 58994583, compound

HRID 1508104Notes

Reaction equation

HRID 1508104 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.CCCCC.[C:41]([O:45][CH2:46][CH3:47])(=[O:44])[CH:42]=[O:43].C1(C)C=CC=CC=1>C1COCC1>[CH2:46]([O:45][C:41](=[O:44])[CH:42]([C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[NH:15][C:14]([C:16]#[N:17])=[CH:13][N:12]=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)[OH:43])[CH3:47]

Participants

8

Reactant 6

HCID 1140TolueneHCID 8003PentaneHCID 70211Ethyl oxoacetateHCID 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 58994583HCID 58994583, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of 4-cyano-1H-imidazole-2-carboxylic acid [4-bromo-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide (71 mg, 0.18 mmol) (as prepared in Example 14, step (c)) in 3 mL THF at −40° C. was added a 2M solution of isopropylmagnesium chloride (i-PrMgCl) in THF (0.23 mL, 0.46 mmol) and the solution was then warmed to 0° C. and stirred for 10 min. The solution was then cooled to −78° C. and a 1.7 M solution of t-BuLi in pentane (0.28 mL, 0.48 mmol) was added dropwise and then a 40% solution of ethyl glyoxalate in toluene (0.23 mL, 0.90 mmol) was added immediately thereafter. After 5 min at −78° C. the reaction was quenched with satd NH4Cl (10 mL) and extracted with EtOAc (3×10 mL) and dried over Na2SO4 and concentrated in vacuo. The title compound was purified by flash chromatography (silica gel) eluting with 50-100% EtOAc/hexanes to give 37 mg (50%) of the title compound as a white solid. Mass spectrum (ESI, m/z): Calcd. for C23H26N4O2, 423.2 (M+H). found 423.1.

Workup

  1. temperatureThe solution was then cooled to −78° C.
  2. customAfter 5 min at −78° C. the reaction was quenched with satd NH4Cl (10 mL)
  3. extractionextracted with EtOAc (3×10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe title compound was purified by flash chromatography (silica gel)
  7. washeluting with 50-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-89a04efff147492293cd09c1de75fb00
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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