Benzenesulfonic Acid → HCID 178429969, compound

HRID 1697048Notes

Reaction equation

HRID 1697048 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.C1([S:46](O)(=[O:48])=[O:47])C=CC=CC=1>C(OCC)(=O)C>[CH2:6]([O:7][SH:46](=[O:48])=[O:47])[C:5]1[CH:25]=[CH:26][CH:2]=[CH:3][CH:4]=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 7371Benzenesulfonic AcidHCID 644241Nilotinib

Product 1

HCID 178429969HCID 178429969, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
76 °C

Procedure

To a 1 L round-bottom flask equipped with a mechanical stirrer, a thermometer, and a condenser, 4 g 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 500 mL of ethyl acetate were charged. The slurry was stirred and heated to 76° C. (reflux) and held at that temperature for 40 minutes. To the resulting clear solution, 7.5 mL of 1 M benzene sulfonic acid solution (in ethyl acetate) was added. The mixture was stirred at 76° C. for 5 hours, cooled down to room temperature by natural cooling (cooling rate ˜0.5° C./min) and held at room temperature for ˜1 hour. 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 mono benzyl sulfonate salt as a yellowish solid. Melting point=˜260° C.; x-ray diffraction pattern showing maxima at 2θ=6.5°, 7.8°, 9.4°, 10.4°, 13.7°, 17.0°, 17.5°, 17.9°, 18.8°, 21.2°.

Workup

  1. customTo a 1 L round-bottom flask equipped with a mechanical stirrer
  2. temperature(reflux)
  3. stirringThe mixture was stirred at 76° C. for 5 hours
  4. temperaturecooled down to room temperature
  5. temperatureby natural cooling
  6. temperature(cooling rate ˜0.5° C./min)
  7. waitheld at room temperature for ˜1 hour
  8. filtrationThe solid was collected by filtration
  9. customwas dried at 50-55° C./10-20 torr for 8-16 hours

Sources & evidence

ORD record
ord-93a3380b7b8448919db6a7416c4ed593
Source dataset
uspto-grants-2012_04
Patent number
US08163904B2

Reaction notes

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