Phosphorous acid → HCID 16006179, compound

HRID 1942209Notes

Reaction equation

HRID 1942209 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.[P:40]([OH:43])([OH:42])[OH:41]>CO>[P:40]([OH:7])([OH:43])([OH:42])=[O:41].[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 107909Phosphorous acidHCID 644241Nilotinib

Product 1

HCID 16006179HCID 16006179, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
64 °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 methanol were charged. The slurry was stirred and heated to 64° C. and held at that temperature for ˜30 minutes. To the resulting clear solution, 7.5 mL of 1 M phosphorous acid solution (in methanol) was added. The mixture was stirred at 64° C. for one hour, cooled down to room temperature by natural cooling (cooling rate ˜0.5° C./min) and held at room temperature for 3-4 hours. The solid was collected by filtration and was dried at 50-55° C./10-20 ton 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 monophosphate salt (3.25 g) as a white solid. Melting point=˜208° C. (dec.); x-ray diffraction pattern showing maxima at 2θ=6.1°, 7.5°, 9.1°, 15.8°, 17.5°, 18.3°, 21.8°, 23.1°, 24.9°, 26.6°.

Workup

  1. customTo a 1 L round-bottom flask equipped with a mechanical stirrer
  2. stirringThe mixture was stirred at 64° C. for one hour
  3. temperaturecooled down to room temperature
  4. temperatureby natural cooling
  5. temperature(cooling rate ˜0.5° C./min)
  6. waitheld at room temperature for 3-4 hours
  7. filtrationThe solid was collected by filtration
  8. customwas dried at 50-55° C./10-20 ton for 8-16 hours

Sources & evidence

ORD record
ord-f91f9496b0cc4a6bbdcc98f49f4f1c90
Source dataset
uspto-grants-2013_03
Patent number
US08389537B2

Reaction notes

Loading…