p-Toluenesulfonic acid → HCID 16006384, compound

HRID 1942212Notes

Reaction equation

HRID 1942212 reaction equation
[CH3:1][C:2]1[CH:26]=[CH:25][C:5]([C:6]([NH:8][C:9]2[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[C:11]([N:19]3[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]3)[CH:10]=2)=[O:7])=[CH:4][C:3]=1[NH:27][C:28]1[N:33]=[C:32]([C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[CH:31]=[CH:30][N:29]=1.[C:40]1([CH3:50])[CH:45]=[CH:44][C:43]([S:46]([OH:49])(=[O:48])=[O:47])=[CH:42][CH:41]=1>C(OCC)(=O)C>[C:40]1([CH3:50])[CH:41]=[CH:42][C:43]([S:46]([OH:49])(=[O:47])=[O:48])=[CH:44][CH:45]=1.[CH3:1][C:2]1[CH:26]=[CH:25][C:5]([C:6]([NH:8][C:9]2[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=[C:11]([N:19]3[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]3)[CH:10]=2)=[O:7])=[CH:4][C:3]=1[NH:27][C:28]1[N:33]=[C:32]([C:34]2[CH:35]=[N:36][CH:37]=[CH:38][CH:39]=2)[CH:31]=[CH:30][N:29]=1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 644241Nilotinib

Product 1

HCID 16006384HCID 16006384, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
76 °C

Procedure

To a 75 mL reactor equipped with a temperature probe and a condenser, 305.6 mg of 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide free base and 30 mL of ethyl acetate were charged. The slurry was stirred and heated to 76° C. To the solution, 580 μL of 1 M p-toluene sulfonic acid solution (in ethyl acetate) was added. The mixture was stirred at 76° C. for six hours, cooled to 25° C. at a rate of 0.5° C./minute and held at 25° C. overnight. The solid was collected by filtration and was dried at 50-55° C./10-20 torr for 8-16 hours to obtain 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide p-toluene sulfonate salt (˜250 mg) as a white solid. Melting point=˜187° C.; x-ray diffraction pattern showing maxima at 2θ=7.3°, 15.4°, 16.1°, 17.5°, 18.3°, 19.0°, 19.7°, 22.5°.

Workup

  1. additionwere charged
  2. stirringThe mixture was stirred at 76° C. for six hours
  3. temperaturecooled to 25° C. at a rate of 0.5° C./minute
  4. filtrationThe solid was collected by filtration
  5. customwas dried at 50-55° C./10-20 torr for 8-16 hours

Sources & evidence

ORD record
ord-ca4de55a6d1d4efaa3c267250a4154cc
Source dataset
uspto-grants-2013_03
Patent number
US08389537B2

Reaction notes

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