Trifluoroacetic acid → N-(3-fluoro-4-(3-(3-(methylcarbamoyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 2241263Notes

Reaction equation

HRID 2241263 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:37]([C:46]2[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=2)[C:38]([C:40]2([C:43]([NH2:45])=[O:44])[CH2:42][CH2:41]2)=[O:39])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[N:15](CC3C=CC(OC)=CC=3)[N:16]=[C:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24](=[O:27])[NH:25][CH3:26])[CH:19]=3)[C:10]=12.C(O)(C(F)(F)F)=O>>[F:1][C:2]1[CH:3]=[C:4]([N:37]([C:46]2[CH:47]=[CH:48][C:49]([F:52])=[CH:50][CH:51]=2)[C:38]([C:40]2([C:43]([NH2:45])=[O:44])[CH2:42][CH2:41]2)=[O:39])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[NH:15][N:16]=[C:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24](=[O:27])[NH:25][CH3:26])[CH:19]=3)[C:10]=12

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68517924N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(3-(methylcarbamoyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Product 1

HCID 178485322N-(3-fluoro-4-(3-(3-(methylcarbamoyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 65.2%

Conditions

Temperature
70 °C

Procedure

A stirred mixture of N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(3-(methylcarbamoyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (35 mg, 0.050 mmol) and TFA (0.5 mL) was heated to 70° C. for 3 hours, or until reaction was complete as determined by LC/MS. The mixture was concentrated in vacuo, using toluene (2×5 mL) to azeotrope residual TFA. The crude was purified by silica gel column chromatography (Biotage 12M) eluting with 1-10% MeOH/CHCl3 to give the desired product as off-white solid (19 mg, 55%). 1H NMR (400 MHz, DMSO-d6) δ 14.03 (s, 1H), 10.39 (s, 1H), 10.00 (s, 1H), 8.49 (s, 2H), 8.38 (d, 1H), 8.12 (d, 1H), 7.87 (m, 2H), 7.64 (m, 2H), 7.55 (t, 1H), 7.47 (m, 2H), 7.15 (t, 2H), 6.32 (d, 1H), 2.78 (d, 3H), 1.47 (d, 4H). LRMS (APCI pos) m/e 583.1 (M+H).

Workup

  1. customuntil reaction
  2. concentrationThe mixture was concentrated in vacuo
  3. customThe crude was purified by silica gel column chromatography (Biotage 12M)
  4. washeluting with 1-10% MeOH/CHCl3

Sources & evidence

ORD record
ord-321dbe2978f5475fbda6772a9e1c1bbd
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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