Trifluoroacetic acid → N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(piperidin-4-ylmethyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamide

HRID 2241433Notes

Reaction equation

HRID 2241433 reaction equation
[F:1][C:2]1[CH:40]=[C:39]([NH:41][C:42]([C:44]2[C:49](=[O:50])[N:48]([C:51]3[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=3)[CH:47]=[CH:46][N:45]=2)=[O:43])[CH:38]=[CH:37][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[N:11]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[N:12]=[C:13]([CH2:14][CH:15]3[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]3)[C:6]=12.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:40]=[C:39]([NH:41][C:42]([C:44]2[C:49](=[O:50])[N:48]([C:51]3[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=3)[CH:47]=[CH:46][N:45]=2)=[O:43])[CH:38]=[CH:37][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[N:11]([CH2:28][C:29]3[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=3)[N:12]=[C:13]([CH2:14][CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[C:6]=12

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68514395tert-butyl 4-((4-(2-fluoro-4-(4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamido)phenoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl)piperidine-1-carboxylate

Product 1

HCID 68515107N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(piperidin-4-ylmethyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolved tert-butyl 4-((4-(2-fluoro-4-(4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamido)phenoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl)piperidine-1-carboxylate (43 mg, 0.055 mmol) in DCM (1 mL) and added excess TFA (d 1.48) (0.100 ml). The mixture was stirred at room temperature for 18 hours. The solvent was removed, and the crude was partitioned between DCM (15 mL) and aqueous 10% Na2CO3 (20 mL). The organic layer was washed with brine, dried over sodium sulfate and evaporated to afford title compound as free-base. Yield 41 mg, 89% purity by HPLC, 97%. LRMS (APCI pos) m/e 678.3 (M+H).

Workup

  1. customThe solvent was removed
  2. customthe crude was partitioned between DCM (15 mL) and aqueous 10% Na2CO3 (20 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated

Sources & evidence

ORD record
ord-607b7622711d4479a573be936c371d64
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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