Methanol → HCID 86624325, compound

HRID 1993705Notes

Reaction equation

HRID 1993705 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:17][C:18]([NH:20][C:21]2[C:22]([CH3:43])=[N:23][C:24]([N:27]3[CH2:32][CH2:31][N:30]([C:33](=[O:42])[C:34]4[C:39]([F:40])=[CH:38][CH:37]=[CH:36][C:35]=4[F:41])[CH2:29][CH2:28]3)=[CH:25][CH:26]=2)=[O:19])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].CO.[CH3:46][S:47]([OH:50])(=[O:49])=[O:48]>C(OCC)(=O)C>[CH3:46][S:47]([OH:50])(=[O:49])=[O:48].[C:1]([C:5]1[CH:6]=[C:7]([NH:17][C:18]([NH:20][C:21]2[C:22]([CH3:43])=[N:23][C:24]([N:27]3[CH2:32][CH2:31][N:30]([C:33](=[O:42])[C:34]4[C:35]([F:41])=[CH:36][CH:37]=[CH:38][C:39]=4[F:40])[CH2:29][CH2:28]3)=[CH:25][CH:26]=2)=[O:19])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 16061458HCID 16061458, compound

Product 1

HCID 86624325HCID 86624325, compoundYield 95.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Charge 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{6-[4-(2,6-difluoro-benzoyl)-piperazin-1-yl]-2-methyl-pyridin-3-yl}-urea (1.00 equiv, 600.67 mmol, 353.00 g), and methanol (3.50 L) to a 5 L flask. Heat the mixture was to 50-60° C. Add methanesulfonic acid (1.00 equiv, 603.49 mmol, 39.56 mL, 58.00 g) in 250 mL of ethyl acetate drop wise. Stir the solution for 0.5 hour at ˜50° C., then remove heating source. Stir for 5 hours, then filter. Concentrate filtrate under reduced pressure. Add ethyl acetate (300 mL) and concentrate under reduced pressure. Add an additional 300 mL of ethyl acetate was added concentrate under reduced pressure. Add 2 L of diethyl ether then stir for 15 minutes. Allow to stand overnight. Stir for 3 hours then filter. Rinse diethyl ether and heptane, then dry under reduced pressure at ˜40° C. to afford the title compound (391.4 g).

Workup

  1. temperatureHeat the mixture
  2. customwas to 50-60° C
  3. customremove
  4. temperatureheating source
  5. stirringStir for 5 hours
  6. filtrationfilter
  7. concentrationAdd ethyl acetate (300 mL) and concentrate under reduced pressure
  8. additionAdd an additional 300 mL of ethyl acetate
  9. additionwas added
  10. concentrationconcentrate under reduced pressure
  11. additionAdd 2 L of diethyl ether
  12. stirringthen stir for 15 minutes
  13. waitAllow to stand overnight
  14. stirringStir for 3 hours
  15. filtrationthen filter
  16. dry with materialRinse diethyl ether and heptane, then dry under reduced pressure at ˜40° C.

Sources & evidence

ORD record
ord-d76c14dcebf843cba3cc4e3d31f07d51
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

Loading…