Methyl iodide → HCID 71255750, compound

HRID 1507646Notes

Reaction equation

HRID 1507646 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([S:13]([CH3:16])(=[O:15])=[O:14])=[N:10][C:9]=2[C:17]([NH:19][C:20]2[CH:36]=[CH:35][C:23]([O:24][C:25]3[CH:30]=[CH:29][N:28]=[C:27]([C:31]([NH:33][CH3:34])=[O:32])[CH:26]=3)=[CH:22][CH:21]=2)=[O:18])=[CH:4][CH:3]=1.[C:37]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:37])[C:11]([S:13]([CH3:16])(=[O:15])=[O:14])=[N:10][C:9]=2[C:17]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([O:24][C:25]3[CH:30]=[CH:29][N:28]=[C:27]([C:31]([NH:33][CH3:34])=[O:32])[CH:26]=3)=[CH:35][CH:36]=2)=[O:18])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 178485505HCID 178485505, compound

Product 1

HCID 71255750HCID 71255750, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a chilled solution of 4-(4-(5-(4-fluorophenyl)-2-(methylsulfonyl)-1H-imidazole-4-carboxamido)phenoxy)-N-methylpicolinamide (200 mg, 0.39 mmol) and K2CO3 (119 mg, 0.86 mmol) in DMF (3.9 mL), was added methyl iodide (29 μL, 67 mg, 0.47 mmol). The reaction mixture was allowed to warm to room temperature and stirred overnight. TLC indicates completion of reaction with a single major product. Solvent was removed under reduced pressure and the crude material was dissolved in H2O (20 mL) and extracted with EtOAc (3×10 mL). The organic fractions were dried over Na2SO4 and concentrated. The crude material was purified by SiO2 chromatography (DCM/MeOH from 100% DCM to 94% DCM/6% MeOH, the desired product elutes in 97% DCM/3% MeOH) to yield a white solid (149 mg, 72% yield). 1HNMR (400 MHz, CDCl3): δ 8.88 (s, 1H), 8.33 (d, 1H, J=6.0 Hz), 7.97 (m, 1H), 7.66 (m, 3H), 7.50 (m, 1H), 7.43 (m, 2H), 7.22 (t, 2H, J=8.4 Hz), 7.03 (d, 2H, J=9.2 Hz), 3.79 (s, 3H), 3.50 (s, 3H), 2.98 (d, 3H, J=5.2 Hz). MS (ESI): m/z 524.0 [M+H]+

Workup

  1. customcompletion of reaction with a single major product
  2. customSolvent was removed under reduced pressure
  3. dissolutionthe crude material was dissolved in H2O (20 mL)
  4. extractionextracted with EtOAc (3×10 mL)
  5. dry with materialThe organic fractions were dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude material was purified by SiO2 chromatography (DCM/MeOH from 100% DCM to 94% DCM/6% MeOH

Sources & evidence

ORD record
ord-3ceae960bdec4eff80057f90ae6ae41f
Source dataset
uspto-grants-2015_12
Patent number
US09221805B2

Reaction notes

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