Trifluoroacetic acid → HCID 59304290, compound

HRID 2241418Notes

Reaction equation

HRID 2241418 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:39])[N:29]([C:33]6[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=6)[N:30]=[CH:31][CH:32]=5)=[O:26])=[CH:20][C:19]=4[F:40])=[C:11]3[C:10]([NH:41][CH:42]3[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]3)=[N:9]2)=CC=1.FC(F)(F)C(O)=O>>[F:40][C:19]1[CH:20]=[C:21]([NH:24][C:25]([C:27]2[C:28](=[O:39])[N:29]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=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]([NH:41][CH:42]3[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]3)[C:11]=12

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68516356HCID 68516356, compound

Product 1

HCID 59304290HCID 59304290, compoundYield 86.9%

Conditions

Temperature
60 °C

Procedure

A stirred mixture of N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-oxo-2-(pyridin-2-yl)-2,3-dihydropyridazine-4-carboxamide (0.014 g, 0.02072 mmol) and 2,2,2-trifluoroacetic acid (TFA) (0.1596 ml, 2.072 mmol) was heated to 60° C. for 18 hours under N2. The mixture was concentrated in vacuo using toluene (3×5 mL) to azeotrope residual TFA. The residue was partitioned between saturated aqueous NaHCO3 and EtOAc. The phases were separated, and the organic phase washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was triturated with ether and decanted to obtain the product as a brown powder (10 mg, 86%). LRMS (apci pos): >99% purity, 220 nm, m/z 556 (M+H); 1H NMR (400 MHz, CDCl3) δ 11.77 (s, 1H), 8.74 (m, 1H), 7.44 (d, 1H), 8.28 (d, 1H), 8.02 (m, 2H), 7.66 (d, 1H), 7.53 (t, 1H), 7.42 (m, 1H), 7.24 (m, 1H), 6.10 (br s, 1H), 4.55 (bd, 1H), 3.80 (br s, 1H), 3.16 (br s, 2H), 2.44 (m, 10H); 19F NMR (376 MHz, CDCl3) δ −125.2 (m).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customThe residue was partitioned between saturated aqueous NaHCO3 and EtOAc
  3. customThe phases were separated
  4. washthe organic phase washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated with ether
  9. customdecanted

Sources & evidence

ORD record
ord-dd0c83b626c6473793bf2d26ff67699e
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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