Imidazole → HCID 72203008, compound

HRID 629057Notes

Reaction equation

HRID 629057 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[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:22]1[CH:26]=[CH:25][N:24]=[CH:23]1.N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>[Cu]I.CS(C)=O>[N:22]1([C:2]2[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=2)[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:26]=[CH:25][N:24]=[CH:23]1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 2678266877040-37-4

Product 1

HCID 72203008HCID 72203008, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

3-Iodo-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 1.1, 204 mg, 0.5 mmol), 1H-imidazole (68.1 mg, 1 mmol), CuI (9.52 mg, 0.050 mmol), L-proline (11.51 mg, 0.100 mmol), K2CO3 (138 mg, 1.000 mmol) and DMSO (500 μL) were added to a vial, which was sealed, evacuated/purged with argon and the RM stirred at 90° C. for 70 h. The RM was diluted with DCM/EtOAc, filtered and stirred with of Chelex® 100 (950 mg). The mixture was washed with sat. aq. Na2CO3, brine, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 12 g, DCM/MeOH+1% NH4OH from 2% B to 10% MeOH+1% NH4OH) to afford the title compound as an off white powder. UPLC-MS (Condition 1) tR=1.55 min, m/z=348 [M+H]+, m/z=346.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.16 (s, 1H) 7.40 (d, J=8.8 Hz, 2H) 7.69 (t, J=7.9 Hz, 1H) 7.85-7.93 (m, 2H) 7.90 (d, J=9.0 Hz, 3H) 8.18 (s, 1H) 8.37 (s, 1H) 10.52 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. additionThe RM was diluted with DCM/EtOAc
  4. filtrationfiltered
  5. stirringstirred with of Chelex® 100 (950 mg)
  6. washThe mixture was washed with sat. aq. Na2CO3, brine
  7. dry with materialdried over MgSO4
  8. customthe solvent was evaporated off under reduced pressure
  9. customto give the crude product which
  10. customwas purified by flash chromatography (Silica gel column, 12 g, DCM/MeOH+1% NH4OH from 2% B to 10% MeOH+1% NH4OH)

Sources & evidence

ORD record
ord-21c8283ee76e4f5dbf05c2ee839f51a4
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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