Trifluoroacetic acid → HCID 178522229, compound
Reaction equation
[F:1][C:2]1[CH:39]=[C:38]([NH:40][C:41]([C:43]2[C:44](=[O:56])[N:45]([C:49]3[CH:54]=[CH:53][C:52]([F:55])=[CH:51][CH:50]=3)[N:46]=[CH:47][CH:48]=2)=[O:42])[CH:37]=[CH:36][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[N:11](CC3C=CC(OC)=CC=3)[N:12]=[C:13]([CH:14]3[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]3)[C:6]=12.C(O)(C(F)(F)F)=O>>[F:1][C:2]1[CH:39]=[C:38]([NH:40][C:41]([C:43]2[C:44](=[O:56])[N:45]([C:49]3[CH:50]=[CH:51][C:52]([F:55])=[CH:53][CH:54]=3)[N:46]=[CH:47][CH:48]=2)=[O:42])[CH:37]=[CH:36][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[NH:11][N:12]=[C:13]([CH:14]3[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]3)[C:6]=12Participants
Conditions
- Temperature
- 80 °C
Procedure
A 50 mL round-bottomed flask was charged with tert-butyl 4-(4-(2-fluoro-4-(2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamido)phenoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidine-1-carboxylate (30.0 mg, 0.0393 mmol) (Example 105, step D) and CF3COOH (5 mL). The reaction mixture was stirred at 80° C. overnight. Then the solvent was removed and the residue was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product (19.5 mg, 91.3%). LRMS (APCI pos): >99% purity, 254 nm, m/e 544 (M+1). 1H NMR (400 MHz, CDCl3+CD3OD, 50/50, v/v) δ 11.94 (s, 1H), 8.42 (m, 1H), 8.28 (m, 2H), 8.00 (m, 1H), 7.62 (m, 2H), 7.46 (m, 1H), 7.35 (m, 1H), 7.24-7.32 (m, 2H), 6.16 (d, 1H), 3.64 (m, 1H), 3.50 (m, 2H), 3.14 (m, 2H), 2.38 (m, 2H), 2.25 (m, 2H).
Workup
- customThen the solvent was removed
- customthe residue was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1
Sources & evidence
- ORD record
- ord-282d1bc947984b7b82aeed8a63d89d88
- Source dataset
- uspto-grants-2010_05
- Patent number
- US07723330B2
Reaction notes
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