Potassium Carbonate → methyl 2-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-[(methylamino)carbonyl]benzoate

HRID 1867111Notes

Reaction equation

HRID 1867111 reaction equation
[Br:1][C:2]1[C:3](=[O:24])[N:4]([C:10]2[CH:19]=[C:18]([C:20]([NH:22][CH3:23])=[O:21])[CH:17]=[CH:16][C:11]=2[C:12]([O:14][CH3:15])=[O:13])[C:5]([CH3:9])=[CH:6][C:7]=1[OH:8].C([O-])([O-])=O.[K+].[K+].[F:31][C:32]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:33]=1[CH2:34]Br>CN(C)C=O.C(OCC)(=O)C.[Cl-].[Na+].O>[Br:1][C:2]1[C:3](=[O:24])[N:4]([C:10]2[CH:19]=[C:18]([C:20]([NH:22][CH3:23])=[O:21])[CH:17]=[CH:16][C:11]=2[C:12]([O:14][CH3:15])=[O:13])[C:5]([CH3:9])=[CH:6][C:7]=1[O:8][CH2:34][C:33]1[CH:36]=[CH:37][C:38]([F:40])=[CH:39][C:32]=1[F:31]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 54724189Methyl 2-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-[(methylamino)carbonyl]benzoate

Product 1

HCID 22050249methyl 2-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-[(methylamino)carbonyl]benzoate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of methyl 2-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-[(methylamino)carbonyl]benzoate (from Step 3) (241 mg, 0.610 mmol) in dimethylformamide (0.5 mL) was added sequentially K2CO3 (240 my, 1.73 mmol) and 2,4 difluorobenzyl bromide (0.085 mL, 0.66 mmol). The resulting suspension was stirred for 6.5 hours until complete consumption of starting material by LCMS analysis. The reaction was then diluted with ethyl acetate (200 mL) and brine washed (3×200 mL). The resulting organic extract was Na2SO4 dried, filtered, and concentrated in vacuo to approximately 5 mL volume. The resulting mother liquor rapidly precipitated and furnished an amorphous solid that was collected. 1H NMR (400 MHz, d4-MeOH) δ 8.22 (d, J=8.2 Hz, 1H), 8.03 (dd, J=8.2, 1.7 Hz, 1H), 7.71 (d, J=1.8 Hz, 1H), 7.67 (app q, J=8.3 Hz, 1H), 7.05 (app t, J=8.6 Hz, 2H), 6.64 (s, 1H), 5.37 (s, 2H), 3.74 (s, 3H), 2.90 (s, 3H), 2.01 (s, 3H) LC/MS C-18 column, tr=2.87 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 521 (M+H). ES-HRMS m/z 521.0491 (M+H calcd for C23H20BrF2N2O5 requires 521.0518).

Workup

  1. washwashed (3×200 mL)
  2. extractionThe resulting organic extract
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo to approximately 5 mL volume
  6. customThe resulting mother liquor rapidly precipitated
  7. customfurnished an amorphous solid
  8. customthat was collected
  9. custom1H NMR (400 MHz, d4-MeOH) δ 8.22 (d, J=8.2 Hz, 1H), 8.03 (dd, J=8.2, 1.7 Hz, 1H), 7.71 (d, J=1.8 Hz, 1H), 7.67 (app q, J=8.3 Hz, 1H), 7.05 (app t, J=8.6 Hz, 2H), 6.64 (s, 1H), 5.37 (s, 2H), 3.74 (s, 3H), 2.90 (s, 3H), 2.01 (s, 3H) LC/MS C-18 column, tr=2.87 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.)

Sources & evidence

ORD record
ord-48f3175ba79a4ac7ad04fc2cd7690961
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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