Trifluoroacetic acid → HCID 178437159、化合物

HRID 1621449ノート

反応式

HRID 1621449 の反応式
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[C:15]([C:16]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][N:20]4C3CCCCO3)=[CH:14][C:13]([CH:32]=[CH2:33])=[CH:12][N:11]=2)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[C:15]([C:16]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][NH:20]4)=[CH:14][C:13]([CH:32]=[CH2:33])=[CH:12][N:11]=2)=[CH:5][CH:4]=1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 59548466N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine

生成物 1

HCID 178437159HCID 178437159、化合物収率 111%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

N-(6-Methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine (76.3 mg, 0.172 mmol) was dissolved in DCM (2.9 mL) and trifluoroacetic acid (Aldrich, St. Louis, Mo., hplc grade, 0.60 mL, 7.8 mmol) was added via syringe. The reaction was stirred at room temperature for 35 minutes, concentrated, treated with MeOH, and filtered. The solid was washed with Et2O, but was not sufficiently (>95% by HPLC) pure. So, the solid and filtrate were combined, concentrated, treated with 2N ammonia in MeOH, and concentrated again. The material was treated with Et2O, but this did not precipitate product. So, it was concentrated, treated with water, and filtered. The solid was washed with water, but was still not 95% pure. So, the solid was collected and purified on HPLC (10% to 100% MeCN/water over 30 minutes using a total flow rate of 100 mL/min) to afford N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-vinylpyridin-2-amine (68.6 mg). MS (ESI pos. ion) m/z 360 (M+H)+. 1H NMR (d6-DMSO) δ 12.70 (s, 1H), 9.98 (s, 1H), 8.65 (s, 1H), 8.55 (d, J=2.54 Hz, 1H), 8.40 (d, J=2.35 Hz, 1H), 8.19 (dd, J=8.8 Hz, 2.74 Hz, 1H), 6.86 (d, J=8.8 Hz, 1H), 6.79 (dd, J=17.5 Hz, 10.9 Hz, 1H), 5.78 (d, J=16.4 Hz, 1H), 5.26 (d, J=11.0 Hz, 1H), 3.85 (s, 3H), 2.86 (s, 3H).

後処理

  1. concentrationconcentrated
  2. additiontreated with MeOH
  3. filtrationfiltered
  4. washThe solid was washed with Et2O
  5. concentrationconcentrated
  6. additiontreated with 2N ammonia in MeOH
  7. concentrationconcentrated again
  8. additionThe material was treated with Et2O
  9. customthis did not precipitate product
  10. concentrationSo, it was concentrated
  11. additiontreated with water
  12. filtrationfiltered
  13. washThe solid was washed with water
  14. customSo, the solid was collected
  15. custompurified on HPLC (10% to 100% MeCN/water over 30 minutes

出典と根拠

ORDレコード
ord-c5e6b57e85df4dcb91c97822ecacd72e
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

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