Trifluoroacetic acid → N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

HRID 2241317Notes

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][CH:45]([N:48]([CH3:50])[CH3:49])[CH2:44][CH2:43]3)=[N:9]2)=CC=1.C(O)(C(F)(F)F)=O>>[CH3:49][N:48]([CH3:50])[CH:45]1[CH2:44][CH2:43][N:42]([C:10]2[C:11]3[C:12](=[N:13][CH:14]=[CH:15][C:16]=3[O:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]4[C:28](=[O:40])[N:29]([C:33]5[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=5)[N:30]=[CH:31][CH:32]=4)=[O:26])=[CH:20][C:19]=3[F:41])[NH:8][N:9]=2)[CH2:47][CH2:46]1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 68513227N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

Product 1

HCID 59304264N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamideYield 66.7%

Conditions

Temperature: 80 °C

Procedure

A 50 mL round-bottomed flask was charged with N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (33.1 mg, 0.0468 mmol) 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 the product (18.3 mg, 66.6%). LRMS (APCI pos): >99% purity, 254 nm, m/e 587 (M+1). 1H NMR (400 MHz, CDCl3) δ 11.83 (s, 1H), 10.80 (s, 1H), 8.42 (d, 1H), 8.28 (d, 1H), 8.24 (m, 1H), 7.98 (dd, 1H), 7.60 (m, 2H), 7.41 (d, 1H), 7.21-7.33 (m, 3H), 6.20 (d, 1H), 4.12 (m, 2H), 2.91 (m, 2H), 2.63 (m, 1H), 2.47 (s, 6H), 2.01 (m, 2H), 1.80 (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-c41cd223154a49ba94a0eb56bdbd6401
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723330B2

Reaction notes

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