Trifluoroacetic acid → HCID 136338260, compound
Reaction equation
[F:1][C@@H:2]1[CH2:7][CH2:6][N:5](C(OCC2C=CC=CC=2)=O)[CH2:4][C@H:3]1[O:18][C:19]1[N:24]=[C:23]([O:25]CC2C=CC(OC)=CC=2)[CH:22]=[C:21]([C:35]2[C:43]3[C:38](=[CH:39][CH:40]=[C:41]([C:44]4[S:45][CH:46]=[CH:47][N:48]=4)[CH:42]=3)[N:37](C3CCCCO3)[N:36]=2)[N:20]=1.[C:55]([OH:61])([C:57]([F:60])([F:59])[F:58])=[O:56]>>[F:58][C:57]([F:60])([F:59])[C:55]([OH:61])=[O:56].[F:1][C@@H:2]1[CH2:7][CH2:6][NH:5][CH2:4][C@H:3]1[O:18][C:19]1[NH:24][C:23](=[O:25])[CH:22]=[C:21]([C:35]2[C:43]3[C:38](=[CH:39][CH:40]=[C:41]([C:44]4[S:45][CH:46]=[CH:47][N:48]=4)[CH:42]=3)[NH:37][N:36]=2)[N:20]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
A glass microwave reaction vessel was charged with benzyl trans-4-fluoro-3-((4-((4-methoxybenzyl)oxy)-6-(1-(tetrahydro-2H-pyran-2-yl)-5-(thiazol-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)oxy)piperidine-1-carboxylate (racemic) (200 mg, 0.26 mmol) and TFA (2 mL). The reaction was stirred and heated in a microwave reactor at 100° C. for 30 min, then cooled to RT. The solvent was removed and the residue was purified with preparative HPLC (20-100% MeCN in water with 0.1% TFA) to give 2-((trans-4-fluoropiperidin-3-yl)oxy)-6-(5-(thiazol-2-yl)-1H-indazol-3-yl)pyrimidin-4(3H)-one trifluoroacetate (racemic) (20 mg, 15%) as a off white solid. MS (ESI, pos. ion) m/z: 412.8 (M+1); 1H NMR (400 MHz, DMSO-d6): δ 13.90 (s, 1 H), 8.96 (brs, 3 H), 8.07 (d, 1 H, J=9.2 Hz), 7.95 (t, 1 H, J=2.4 Hz), 7.75-7.79 (m, 2 H), 5.63 (s, 1 H), 5.05-5.20 (m, 1 H), 3.70-3.72 (m, 1 H), 3.28-3.40 (m, 1 H), 3.16-3.23 (m, 2 H), 2.15-2.30 (m, 3 H).
Workup
- customA glass microwave reaction vessel
- temperaturecooled to RT
- customThe solvent was removed
- customthe residue was purified with preparative HPLC (20-100% MeCN in water with 0.1% TFA)
Sources & evidence
- ORD record
- ord-2f694d51df724ee29d219c54d3073bb0
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09090593B2
Reaction notes
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