Trifluoroacetic acid → HCID 24876601, compound

HRID 2241300Notes

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:28](=[O:40])[N:29]([C:33]6[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=6)[N:30]=[CH:31][CH:32]=5)=[O:26])=[CH:20][C:19]=4[F:41])=[C:11]3[C:10]([N:42]3[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]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:28](=[O:40])[N:29]([C:33]3[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=3)[N:30]=[CH:31][CH:32]=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]([N:42]3[CH2:43][CH2:44][N:45]([CH3:48])[CH2:46][CH2:47]3)[C:11]=12

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 68516252HCID 68516252, compound

Product 1

HCID 24876601HCID 24876601, compoundYield 90.1%

Conditions

Temperature: 60 °C

Procedure

A 50 mL round-bottomed flask was charged with N-(4-(1-(4-methoxybenzyl)-3-(4-methylpiperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (33.2 mg, 0.0489 mmol) and CF3COOH (5 mL). The reaction mixture was stirred at 60° C. until LC-MS showed that the starting material had been consumed (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 (24.6 mg, 90%). LRMS (APCI pos): >99% purity, 254 nm, m/e 559 (M+1). 1H NMR (400 MHz, CDCl3) δ 11.85 (s, 1H), 10.33 (s, 1H), 8.42 (d, 1H), 8.25 (m, 2H), 7.97 (dd, 1H), 7.61 (m, 2H), 7.41 (d, 1H), 7.23-7.30 (m, 3H), 6.20 (d, 1H), 3.56 (m, 4H), 2.69 (m, 4H), 2.40 (s, 3H).

Workup

customhad been consumed (overnight)
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-026ad2eb9cd0495a9362c96b8c3ce649
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723330B2

Reaction notes

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