5-(3-fluoro-4-(3-(4-fluorophenyl)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one → 5-(3-fluoro-4-(3-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

HRID 2241305Notes

Reaction equation

HRID 2241305 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:34]2[C:35](=[O:48])[N:36]([CH3:47])[C:37]([NH:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[N:38][CH:39]=2)[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][C:21]([F:24])=[CH:20][CH:19]=3)[C:10]=12>C(O)(C(F)(F)F)=O>[F:1][C:2]1[CH:3]=[C:4]([C:34]2[C:35](=[O:48])[N:36]([CH3:47])[C:37]([NH:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[N:38][CH:39]=2)[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:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[C:10]=12

Participants

3

Reactant 1

HCID 685153815-(3-fluoro-4-(3-(4-fluorophenyl)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Product 1

HCID 1784812015-(3-fluoro-4-(3-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
60 °C

Procedure

5-(3-fluoro-4-(3-(4-fluorophenyl)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (0.024 g, 0.037 mmol) was dissolved in TFA (1 mL) and the reaction mixture was stirred at 60° C. for 3 hours and then at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was partitioned between EtOAc and saturated NaHCO3. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined EtOAc layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 10:1 CH2Cl2/MeOH. The product was obtained (15.2 mg; 78%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 13.97 (br s, 1H), 9.02 (br s, 1H), 8.38 (d, 1H), 8.09 (s, 1H), 8.03 (m, 2H), 7.85 (dd, 1H), 7.69-7.48 (m, 4H), 7.38 (t, 2H), 7.32 (t, 2H), 7.17 (t, 1H), 6.38 (d, 1H), 3.58 (s, 3H). LRMS (APCI pos) m/e 523 (M+1).

Workup

  1. customat room temperature
  2. customovernight
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue was partitioned between EtOAc and saturated NaHCO3
  5. customThe layers were separated
  6. extractionthe aqueous layer was re-extracted with EtOAc (1×)
  7. dry with materialThe combined EtOAc layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by flash column chromatography
  11. washeluting with 10:1 CH2Cl2/MeOH
  12. customThe product was obtained (15.2 mg; 78%) as a yellow solid

Sources & evidence

ORD record
ord-75c513a42f764accbc87a85b43b7366e
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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