N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2-chloro-5-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide → N-(2-chloro-5-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

HRID 2241388Notes

Reaction equation

HRID 2241388 reaction equation
COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[C:23]([F:24])=[CH:22][C:21]([NH:25][C:26]([C:28]5[C:29](=[O:41])[N:30]([C:34]6[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=6)[N:31]=[CH:32][CH:33]=5)=[O:27])=[C:20]([Cl:42])[CH:19]=4)=[C:11]3[C:10]([NH:43][CH:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)=[N:9]2)=CC=1>C(O)(C(F)(F)F)=O>[Cl:42][C:20]1[CH:19]=[C:18]([O:17][C:16]2[CH:15]=[CH:14][N:13]=[C:12]3[NH:8][N:9]=[C:10]([NH:43][CH:44]4[CH2:45][CH2:46][N:47]([CH3:50])[CH2:48][CH2:49]4)[C:11]=23)[C:23]([F:24])=[CH:22][C:21]=1[NH:25][C:26]([C:28]1[C:29](=[O:41])[N:30]([C:34]2[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=2)[N:31]=[CH:32][CH:33]=1)=[O:27]

Participants

3

Reactant 1

HCID 68515015N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2-chloro-5-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

Product 1

HCID 59304315N-(2-chloro-5-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamideYield 41.9%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
50 °C

Procedure

A solution of N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2-chloro-5-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (100 mg, 0.138 mmol) was dissolved in TFA (2 mL) and the solution was heated to 50° C. for 1 hour. Excess TFA was evaporated and the crude material was dissolved in EtOAc. The organic layer washed with saturated aqueous NaHCO3, brine, dried with Na2SO4, filtered and concentrated to afford a yellow solid. The solid washed with diethyl ether to afford the product (35 mg, 41.9% yield) as a yellow solid. LRMS (APCI pos) m/e 607.0 (M+H). 1H NMR (DMSO-d6, 400 MHz) δ 12.32 (s, 1H), 12.22 (s, 1H), 8.70 (d, 1H), 8.42 (dd, 12H), 8.17 (d, 1H), 7.91 (d, 1H), 7.74-7.67 (m, 2H), 7.49-7.41 (m, 2H), 6.17-6.13 (m, 1H), 5.23-5.18 (m, 1H), 3.60-3.42 (m, 1H), 2.85-2.73 (m, 2H), 2.20 (s, 3H), 2.10-1.96 (m, 4H), 1.65-1.53 (m, 2H).

Workup

  1. customExcess TFA was evaporated
  2. dissolutionthe crude material was dissolved in EtOAc
  3. washThe organic layer washed with saturated aqueous NaHCO3, brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a yellow solid
  8. washThe solid washed with diethyl ether

Sources & evidence

ORD record
ord-d5807096ae0248779635c7d15e4e99d1
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

Loading…