Imidazole → HCID 72203014, compound

HRID 629067Notes

Reaction equation

HRID 629067 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[CH3:22])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].[NH:23]1[CH:27]=[CH:26][N:25]=[CH:24]1.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CCOC(C)=O.[Cu]I.CS(C)=O>[N:23]1([C:2]2[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=2[CH3:22])[C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=2)=[O:6])[CH:27]=[CH:26][N:25]=[CH:24]1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 89907516HCID 89907516, compound

Product 1

HCID 72203014HCID 72203014, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 21226138Dichloromethane ethylacetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-iodo-4-methyl-N-(4-(trifluoromethoxy)phenyl)benzamide (100 mg, 0.237 mmol), imidazole (64.6 mg, 0.95 mmol), CuI (9.04 mg, 0.048 mmol), L-proline (10.94 mg, 0.094 mmol), K2CO3 (131.2 mg, 0.95 mmol) and DMSO (250 μL) were stirred under argon for 66 h at 90° C. The RM was cooled to, diluted with DCM/EtOAc, filtered, washed with 10% aq. NaCO3 solution and brine, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® 4 g silica gel, DCM/MeOH+1% NH3 from 0% B to 10% DCM/MeOH+1% NH3) to afford the title compound. UPLC-MS (Condition 2) tR=0.9 min, m/z=362.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.23 (s, 3H) 7.12 (d, J=0.78 Hz, 1H) 7.36 (d, J=8.99 Hz, 2H) 7.49 (d, J=0.78 Hz, 1H) 7.58 (d, J=7.82 Hz, 1H) 7.84-7.90 (m, 2H) 7.90-7.93 (m, 1H) 7.93-7.95 (m, 1H) 7.98 (dd, J=7.82, 1.56 Hz, 1H) 10.41 (s, 1H).

Workup

  1. temperatureThe RM was cooled to,
  2. filtrationfiltered
  3. washwashed with 10% aq. NaCO3 solution and brine
  4. dry with materialdried over MgSO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give a residue which
  7. customwas purified by flash chromatography (RediSep® 4 g silica gel, DCM/MeOH+1% NH3 from 0% B to 10% DCM/MeOH+1% NH3)

Sources & evidence

ORD record
ord-bc9ee903d4bf4e6c8196f7599ec1b452
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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