Methyl iodide → HCID 22050583, compound

HRID 1866975Notes

Reaction equation

HRID 1866975 reaction equation
[K].[Cl:2][C:3]1[C:4](=[O:29])[N:5]([C:19]2[C:26]([OH:27])=[CH:25][C:22]([C:23]#[N:24])=[CH:21][C:20]=2[F:28])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=1[F:18].I[CH3:31]>CN(C)C=O>[Cl:2][C:3]1[C:4](=[O:29])[N:5]([C:19]2[C:26]([O:27][CH3:31])=[CH:25][C:22]([C:23]#[N:24])=[CH:21][C:20]=2[F:28])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=1[F:18]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 5462222PotassiumHCID 22050338HCID 22050338, compound

Product 1

HCID 22050583HCID 22050583, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The potassium salt of 4-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-2-oxopyridin-1(2H)-yl]-3-fluoro-5-hydroxybenzonitrile (from Step 1) (273 mg, 0.614 mmol) was stirred in 5 ml anhydrous dimethylformamide under nitrogen. Iodomethane (93 mg, 0.66 mmol) was added, and stirring continued for 2 hr. The mixture was diluted to 50 ml with ice-cold water, and the white precipitate collected by filtration. The precipitate was washed thrice with water, sucked dry under a blanket of nitrogen, and dried further in vacuo overnight (242 mg, 87%). 1H-NMR (400 MHz, DMSO-d6) δ 7.73 (m, 2H), 7.65 (m, 2H), 7.34 (dt, J=9.90, 2.39 Hz, 1H), 7.17 (dt, J=8.75, 2.47 Hz, 1H), 6.75 (d, J=7.97 Hz, 1H), 5.37 (s, 2H), 3.84 (s, 3H). 19F-NMR (400 MHz, DMSO-d6) δ −109.24 (quintet, J=7.85 Hz, 1F), −113.54 (quartet, J=9.83 Hz, 1F), −118.33 (d, J=7.77 Hz, 1F). LC/MS tr=5.40 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50° C.) ES-MS m/z 421 (M+H). ES-HRMS m/z 421.0522 (M+H calcd for C20H13ClF3N2O3 requires 421.0561).

Workup

  1. additionThe mixture was diluted to 50 ml with ice-cold water
  2. filtrationthe white precipitate collected by filtration
  3. washThe precipitate was washed thrice with water
  4. customsucked dry under a blanket of nitrogen
  5. customdried further in vacuo overnight (242 mg, 87%)
  6. customLC/MS tr=5.40 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 215 nm, at 50° C.) ES-MS m/z 421 (M+H)

Sources & evidence

ORD record
ord-6ef5622857ae48c69360b7153a368c75
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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