Trifluoroacetic acid → HCID 59304261, compound

HRID 2241415Notes

Reaction equation

HRID 2241415 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]([CH2:48][CH2:49][O:50][CH3:51])[CH2:44][CH2:43]3)=[N:9]2)=CC=1.FC(F)(F)C(O)=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[CH2:47][CH2:46][N:45]([CH2:48][CH2:49][O:50][CH3:51])[CH2:44][CH2:43]3)[C:11]=12

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68513921N-(4-(1-(4-methoxybenzyl)-3-(4-(2-methoxyethyl)piperazin-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 59304261HCID 59304261, compoundYield 60%

Conditions

Temperature
60 °C

Procedure

A stirred mixture of N-(4-(1-(4-methoxybenzyl)-3-(4-(2-methoxyethyl)piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (2 mg, 0.002767 mmol), and 2,2,2-trifluoroacetic acid (0.2132 ml, 2.767 mmol) was heated to 60° C. in a sealed vessel for 18 hours. After cooling to ambient temperature, the reaction was concentrated in vacuo, using toluene to azeotrope residual TFA. The resulting residue was dissolved in DCM, and purified by preparative TLC (0.5 mm thickness, Rf=0.50), eluting with 10% MeOH (containing 7N NH3) in DCM. The product was obtained as a pale yellow powder (1 mg, 48%). HPLC: 89% purity (220 nm); LRMS (APCI+): 100% purity, 220 nm, m/z 603 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 11.87 (s, 1H), 9.81 (s, 1H), 8.44 (m, 1H), 8.26 (m, 2H), 7.98 (m, 1H), 7.63 (m, 2H), 7.42 (m, 1H), 7.28 (m, 3H), 6.22 (m, 1H), 3.75 (m, 1H), 3.61 (m, 3H), 3.39 (s, 3H), 2.73 (m, 4H), 1.5-2.2 (m, 4H).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe reaction was concentrated in vacuo
  3. dissolutionThe resulting residue was dissolved in DCM
  4. custompurified by preparative TLC (0.5 mm thickness, Rf=0.50)
  5. washeluting with 10% MeOH (containing 7N NH3) in DCM

Sources & evidence

ORD record
ord-047e06d0875b437888f6befaaef6e119
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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