Hydrazine → 3-bromo-4-[(2,4-difluorobenzyl)oxy]-1-[5-(5-hydroxy-1H-pyrazol-3-yl)-2-methylphenyl]-6-methylpyridin-2(1H)-one

HRID 1867173Notes

Reaction equation

HRID 1867173 reaction equation
[Br:1][C:2]1[C:3](=[O:34])[N:4]([C:19]2[CH:20]=[C:21]([C:26](=O)[CH2:27][C:28](OCC)=[O:29])[CH:22]=[CH:23][C:24]=2[CH3:25])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].O.[NH2:36][NH2:37].NN>CCO.C(O)(=O)C>[Br:1][C:2]1[C:3](=[O:34])[N:4]([C:19]2[CH:20]=[C:21]([C:26]3[CH:27]=[C:28]([OH:29])[NH:37][N:36]=3)[CH:22]=[CH:23][C:24]=2[CH3:25])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

6

Reactant 3

HCID 9321HydrazineHCID 24654Hydrazine hydrate (1:1)2×HCID 22050332ethyl 3-{3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylphenyl}-3-oxopropanoate

Product 1

HCID 1784238403-bromo-4-[(2,4-difluorobenzyl)oxy]-1-[5-(5-hydroxy-1H-pyrazol-3-yl)-2-methylphenyl]-6-methylpyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of ethyl 3-{3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylphenyl}-3-oxopropanoate (from Step 1) (0.20 g, 0.37 mmol) in EtOH (5.00 mL) was added hydrazine hydrate (0.01 mL, 0.41 mmol). The reaction mixture was heated at 60° C. with a condensere. After 1 h, additional hydrazine hydrate (0.01 mL) was added. After 2 h, acetic acid (2 drops) was added. At 4 h, additional hydrazine was added (0.1 mL). At 5 h, the reaction appeared to be complete. Left in fridge overnight. Precipitate filtered, washed with hexane, found to be product, a white solid (0.10 g, 54%). 1H NMR (CD3OD/400 MHz) δ 7.66 (m, 2H), 7.45 (m, 2H), 7.05 (t, 2H, J=9.6 Hz), 6.65 (s, 1H), 5.36 (s, 2H), 2.04 (s, 3H), 2.02 (s, 3H). ESHRMS m/z 502.0552 and 504.0569 (M+H calculated for C23H19BrF2N3O3 requires 502.0572 and 504.0555).

Workup

  1. waitAfter 2 h
  2. waitAt 4 h
  3. waitAt 5 h
  4. waitLeft in fridge overnight
  5. filtrationPrecipitate filtered
  6. washwashed with hexane

Sources & evidence

ORD record
ord-cc2c9f74f2654777bb49d85e4de5654e
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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