Trifluoroacetic acid → HCID 178522228, compound
Reaction equation
COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]5[C:32](=[O:33])[N:31]([C:34]6[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=6)[N:30]=[CH:29][CH:28]=5)=[O:26])=[CH:20][C:19]=4[F:41])=[C:11]3[C:10]([C:42]3[CH2:47][CH2:46][N:45](C(OC(C)(C)C)=O)[CH2:44][CH:43]=3)=[N:9]2)=CC=1.C(O)(C(F)(F)F)=O>>[F:41][C:19]1[CH:20]=[C:21]([NH:24][C:25]([C:27]2[C:32](=[O:33])[N:31]([C:34]3[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=3)[N:30]=[CH:29][CH:28]=2)=[O:26])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:8][N:9]=[C:10]([C:42]3[CH2:47][CH2:46][NH:45][CH2:44][CH:43]=3)[C:11]=12Participants
Conditions
- Temperature
- 60 °C
Procedure
A 50 mL round-bottomed flask was charged with tert-butyl 4-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (38.3 mg, 0.0503 mmol) and CF3COOH (5 mL). The reaction mixture was stirred at 60° C. for 4 hours. 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 give product 21.8 mg, the yield is 80.1%. LRMS (APCI pos): >99% purity, 254 nm, m/e 542 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 11.71 (s, 1H), 8.38 (d, 1H), 8.30 (d, 1H), 8.27 (d, 1H), 8.04 (dd, 1H), 6.82 (m, 2H), 7.59 (d, 1H), 7.49 (m, 1H), 7.42 (m, 2H), 6.69 (s, 1H), 6.31 (d, 1H), 3.39 (m, 2H), 2.94 (m, 2H), 2.58 (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-e54eb215858d404894871d0d6b704f09
- Source dataset
- uspto-grants-2010_05
- Patent number
- US07723330B2
Reaction notes
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