Trifluoroacetic acid → HCID 135968108, compound

HRID 2241427Notes

Reaction equation

HRID 2241427 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]([C:42]3[N:43]([CH3:47])[CH:44]=[CH:45][N:46]=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]([C:42]3[N:43]([CH3:47])[CH:44]=[CH:45][N:46]=3)[C:11]=12

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68515088N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(1-methyl-1H-imidazol-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

Product 1

HCID 135968108HCID 135968108, compoundYield 60.2%

Conditions

Temperature
60 °C

Procedure

N-(4-(1-(4-Methoxybenzyl)-3-(1-methyl-1H-imidazol-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (127 mg, 0.192 mmol) and TFA (2 mL) were charged in a 50 mL single-neck, round-bottomed flask. The reaction mixture was stirred at 60° C. until the starting material had been consumed (overnight). Then the reaction was cooled to room temperature and the CF3COOH was removed under reduced pressure. The residue was partitioned between DCM (50 mL) and saturated NaHCO3 (50 mL). The phases were separated and the aqueous phase was extracted with DCM (3×50 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (62.5 mg, 60.2%). LRMS (APCI pos): >99% purity, 254 nm, m/e 541 (M+1). 1H NMR (400 MHz, DMSO-d6 δ 14.01 (s, 1H), 11.71 (s, 1H), 8.37 (m, 2H), 8.27 (d, 1H), 8.06 (m, 1H), 7.76 (d, 1H), 7.68 (m, 2H), 7.52-7.63 (m, 2H), 7.47 (d, 1H), 7.41 (m, 2H), 6.36 (d, 1H), 3.31 (s, 3H).

Workup

  1. customhad been consumed (overnight)
  2. temperatureThen the reaction was cooled to room temperature
  3. customthe CF3COOH was removed under reduced pressure
  4. customThe residue was partitioned between DCM (50 mL) and saturated NaHCO3 (50 mL)
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with DCM (3×50 mL)
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield a crude product
  11. customThe crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1

Sources & evidence

ORD record
ord-a7892ad0985c495b8638a79f9e1a1d9e
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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