Acetone → LY-2584702 (tosylate salt)

HRID 2194483Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:25]=[CH:24][N:23]=[C:22]5[NH:26][N:27]=[CH:28][C:21]=45)[CH2:16][CH2:15]3)[N:11]([CH3:13])[CH:12]=2)=[CH:4][C:3]=1[C:29]([F:32])([F:31])[F:30].CC(C)=O.O.[C:38]1([CH3:48])[CH:43]=[CH:42][C:41]([S:44]([OH:47])(=[O:46])=[O:45])=[CH:40][CH:39]=1>O>[C:38]1([CH3:48])[CH:39]=[CH:40][C:41]([S:44]([OH:47])(=[O:45])=[O:46])=[CH:42][CH:43]=1.[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:25]=[CH:24][N:23]=[C:22]5[NH:26][N:27]=[CH:28][C:21]=45)[CH2:16][CH2:15]3)[N:11]([CH3:13])[CH:12]=2)=[CH:4][C:3]=1[C:29]([F:31])([F:30])[F:32]

Participants

Conditions

Temperature: 55 °C

Procedure

Dissolve 4-{4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine (20 g, 44.9 mmoles) in a 20:1 H2O:acetone mixture (360 mL). Add a solution of p-toluenesulfonic acid monohydrate (10.25 g; 53.9 mmoles; 1.2 eq) in a 20:1 H2O: acetone mixture (40 mL) to the reaction over 20 minutes at 20° C. Heat the reaction mixture to 55° C., hold for 1 hour, then cool to 25° C. over 1 hour. Filter the solid and wash the cake with water (40 mL). Drying under vacuum at 50° C. affords 4-{4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine p-toluenesulfonate (23.9 g; 86%) as a white solid.

Workup

temperaturecool to 25° C. over 1 hour
filtrationFilter the solid
washwash the cake with water (40 mL)
customDrying under vacuum at 50° C.

Sources & evidence

ORD record: ord-9bdb80fdabbe49e48934306e4a06c0fa
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08334293B2

Reaction notes

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