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 2241305노트

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HRID 2241305 반응식
[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

참가 물질

3

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6422Trifluoroacetic acid용매

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온도
60 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-75c513a42f764accbc87a85b43b7366e
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723330B2

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