Trifluoroacetic acid → HCID 178462544, compound

HRID 2241435Notes

Reaction equation

HRID 2241435 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:32](=[O:33])[N:31]([C:34]6[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=6)[CH:30]=[CH:29][N:28]=5)=[O:26])=[CH:20][C:19]=4[F:41])=[C:11]3[C:10]([CH2:42][CH:43]3[CH2:48][CH2:47][N:46]([CH2:49][CH3:50])[CH2:45][CH2:44]3)=[N:9]2)=CC=1.C(O)(C(F)(F)F)=O>>[CH2:49]([N:46]1[CH2:45][CH2:44][CH:43]([CH2:42][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:32](=[O:33])[N:31]([C:34]5[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=5)[CH:30]=[CH:29][N:28]=4)=[O:26])=[CH:20][C:19]=3[F:41])[NH:8][N:9]=2)[CH2:48][CH2:47]1)[CH3:50]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68517236HCID 68517236, compound

Product 1

HCID 178462544HCID 178462544, compound

Conditions

Temperature
70 °C

Procedure

N-(4-(1-(4-methoxybenzyl)-3-((1-ethylpiperidin-4-yl)methyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamide (18 mg, 0.025 mmol) was added to a small round bottom flask and dissolved in excess TFA (d 1.48) (0.2 ml, 2.550 mmol). The mixture was stirred at 70° C. overnight. The solvent was evaporated, and the crude was chromatographed on Si (preparative TLC) 0.5 mm thickness, eluting with 10% MeOH/DCM w/1% NH4OH. Product isolated and determined to by mono-TFA salt by 19F-NMR. Yield 1.4 mg, 8%. 1H NMR (400 MHz, MeOD) δ 8.29 (d, 1H), 8.08 (d, 1H), 7.93 (d, 1H), 7.79 (d, 2H), 7.60 (m, 2H), 7.54 (br d, 1H), 7.41 (t, 1H), 7.35 (t, 2H), 6.33 (d, 1H), 3.10 (d, 2H), 2.75 (br s, 2H), 2.43 (br s, 2H), 2.11 (br m, 1H), 1.88 (d, 2H), 1.55 (m, 2H), 1.19 (t, 3H). LRMS (APCI pos) m/e 586.3 (M+H).

Workup

  1. customThe solvent was evaporated
  2. customthe crude was chromatographed on Si (preparative TLC) 0.5 mm thickness
  3. washeluting with 10% MeOH/DCM
  4. customProduct isolated

Sources & evidence

ORD record
ord-a286d974366d4eceb3267edede66f8a5
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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