Trifluoroacetic acid → N-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)biphenyl-3-carboxamide

HRID 2241369ノート

反応式

HRID 2241369 の反応式
[F:1][C:2]1[CH:3]=[C:4]([NH:35][C:36]([C:38]2[CH:39]=[C:40]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[CH:41]=[CH:42][CH:43]=2)=[O:37])[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]([NH:18][CH:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[C:10]=12.C(O)(C(F)(F)F)=O>>[F:1][C:2]1[CH:3]=[C:4]([NH:35][C:36]([C:38]2[CH:39]=[C:40]([C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)[CH:41]=[CH:42][CH:43]=2)=[O:37])[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]([NH:18][CH:19]3[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]3)[C:10]=12

参加物

3

反応物 2

HCID 6422Trifluoroacetic acidHCID 68516446N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)biphenyl-3-carboxamide

生成物 1

HCID 59304384N-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)biphenyl-3-carboxamide収率 27.3%

反応条件

温度
50 °C

実験手順

To a flask containing N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)biphenyl-3-carboxamide (10 mg, 0.015 mmol) at room temperature under a drying tube was added TFA (1 mL). The solution was warmed to 50° C. for 3 hours. After cooling to ambient temperature, the solution was concentrated, and the residue was redissolved in 5 mL dichloromethane and stirred rapidly with 5 mL 10% sodium carbonate solution to provide the free base. The organic layer was isolated, dried (MgSO4), filtered and concentrated. The crude product was passed through a small gravity silica cartridge with 95/5 dichloromethane/MeOH to provide the desired product as a clear oil (2.2 mg, 27% yield). 1H NMR (400 MHz, CDCl3) δ 9.40 (br s, 1H), 8.20 (d, 1H), 8.11 (m, 1H), 8.01 (m, 1H), 7.92 (m, 1H), 7.85 (m, 1H), 7.82 (m, 1H), 7.65 (m, 2H), 7.60 (m, 1H), 7.50 (m, 2H), 7.41 (m, 2H), 7.30 (m, 1H), 6.10 (d, 1H), 4.54 (m, 1H), 3.73 (br m, 1H), 2.89 (br m, 2H), 2.34 (s, 3H), 2.24 (br m, 3H), 1.68 (br m, 2H). LCMS (APCI+): m/z 537 (M+1) detected.

後処理

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe solution was concentrated
  3. dissolutionthe residue was redissolved in 5 mL dichloromethane
  4. customto provide the free base
  5. customThe organic layer was isolated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-d9026e4afae04d10a85188b8736b57a9
出典データセット
uspto-grants-2010_05
特許番号
US07723330B2

反応ノート

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