Sulfuric Acid → HCID 10298942, compound

HRID 1261593Notes

Reaction equation

HRID 1261593 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])[CH:5]=[CH:4][C:3]=1[CH:15]([C:20]([C:22]1[N:26]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[N:25]=[C:24]([C:35]([F:38])([F:37])[F:36])[CH:23]=1)=[O:21])C(OC)=O.S(O)(O)(=O)=O>CO>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])[CH:5]=[CH:4][C:3]=1[CH2:15][C:20]([C:22]1[N:26]([C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)[N:25]=[C:24]([C:35]([F:38])([F:37])[F:36])[CH:23]=1)=[O:21]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 11613430HCID 11613430, compound

Product 1

HCID 10298942HCID 10298942, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Part A. To methyl 2-[2-fluoro-4-(2-oxo-1(2H)-pyridinyl)phenyl]-3-[1-(4-methoxyphenyl)-3-(trifluoro-methyl)-1H-pyrazol-5-yl]-3-oxopropanoate (Part H, Example 71) (24 mg, 0.045 mmol) was added methyl alcohol (2.3 mL) and concentrated aqueous dihydrogen sulfate (0.048 mL). The reaction was then warmed to reflux. After 48 h, monitoring by LC/MS (C18 reverse phase, eluted with 0.05% TFA in acetonitrile/water) showed 90% of starting material remaining. An additional 0.80 mL-portion of 4M aqueous dihydrogen sulfate was added, and the reaction was maintained under reflux conditions for 6 h. The reaction was cooled to 0° C., and the resulting white precipitate was filtered to afford 1-(3-fluoro-4-{2-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-2-oxoethyl}phenyl)-2(1H)-pyridinone (11 mg, 52%) as a white solid. LC/MS (ESP+): 472.1 (M+H)+. 1H NMR (enol form) (CD3OD) δ 7.70 (s, 1H), 7.60 (m, 2H), 7.43 (t, 1H), 7.28 (m, 3H), 7.20 (m, 1H), 6.98 (m, 2H), 6.62 (d, 1H), 6.44 (t, 1H), 4.42 (s 0.5H), 4.39 (br s, 0.5H), 3.81 (s, 3H).

Workup

  1. temperatureThe reaction was then warmed to reflux
  2. washmonitoring by LC/MS (C18 reverse phase, eluted with 0.05% TFA in acetonitrile/water)
  3. additionAn additional 0.80 mL-portion of 4M aqueous dihydrogen sulfate was added
  4. temperaturethe reaction was maintained under reflux conditions for 6 h
  5. filtrationthe resulting white precipitate was filtered

Sources & evidence

ORD record
ord-c850e662fe8f4c6a8b1888c811aa0fe4
Source dataset
uspto-grants-2013_06
Patent number
US08470854B2

Reaction notes

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