Toluene-p-sulphonic anhydride → HCID 178427767、化合物

HRID 244160ノート

反応式

HRID 244160 の反応式
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:20]=[C:19]4[C:14]([CH:15]=[CH:16][C:17]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)=[N:18]4)=[CH:13][CH:12]=3)=[CH:9][N:8]([C@H:27]3[CH2:30][C@H:29]([CH2:31][OH:32])[CH2:28]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[O:33](S(C1C=CC(C)=CC=1)(=O)=O)[S:34]([C:37]1[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=1)(=O)=[O:35]>C(Cl)Cl.N1C=CC=CC=1.O.C([O-])(O)=O.[Na+]>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:20]=[C:19]4[C:14]([CH:15]=[CH:16][C:17]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)=[N:18]4)=[CH:13][CH:12]=3)=[CH:9][N:8]([C@H:27]3[CH2:28][C@H:29]([CH2:31][O:32][S:34]([C:37]4[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=4)(=[O:35])=[O:33])[CH2:30]3)[C:4]=2[N:5]=[CH:6][N:7]=1

参加物

7

反応物 2

HCID 77773Toluene-p-sulphonic anhydride2 回HCID 178508594HCID 178508594、化合物

生成物 1

HCID 178427767HCID 178427767、化合物

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒3 回HCID 516892Sodium Bicarbonate溶媒

実験手順

To a suspension of trans-{3-[4-amino-5-(2-phenylquinolin-7-yl)-pyrrolo[2,3-d]pyrimidin-7-yl]-cyclobutyl}-methanol (105.7 mg, 0.251 mmol) in CH2Cl2 (5 mL) and pyridine (1 mL), cooled in a dry ice/acetone bath, was added a solution of Ts2O (92 mg, 0.28 mmol) in CH2Cl2 (2 mL) over 5 min, then the reaction mixture was warmed up to ambient temperature and stirred for 16 h. More Ts2O (70 mg, 0.21 mmol) was added, and stirring at ambient temperature was continued for 4.5 h. The reaction solution was diluted with CH2Cl2 (25 mL), water and saturated NaHCO3 sol. were added, the layers were separated, the aqueous layer was extracted with CH2Cl2 (3×25 mL), and the combined CH2Cl2 extracts were washed with water and brine and dried over MgSO4. Filtration and concentration after adding toluene (10 mL; to remove remaining pyridine as azeotrop) gave the desired product. No purification before the next step. 1H NMR (CDCl3, 400 MHz) δ 2.43-2.51 (m, 2H), 2.47 (s, 2H), 2.67-2.86 (m, 3H), 4.22 (d, J=6.6 Hz, 2H), 5.19 (brs, 2H), 5.36 (quint, J=8.0 Hz, 1H), 7.29 (s, 1H), 7.37-7.41 (m, 2H), 7.46-7.51 (m, 1H), 7.52-7.58 (m, 2H), 7.68 (dd, J=1.8, 8.4 Hz, 1H), 7.83-7.87 (m, 2H), 7.92 (d, J=8.6 Hz, 1H), 7.93 (d, J=8.4 Hz, 1H), 8.17-8.22 (m, 2H), 8.25-8.29 (m, 2H), 8.33 (s, 1H). MS (ES+): m/z 576.1 (54) [MH+], 338.2 (10) [MH+-cyclobutene-CH2OTs]. HPLC: tR=2.8 min (OpenLynx, nonpolar—5 min).

後処理

  1. temperaturecooled in a dry ice/acetone bath
  2. stirringstirring at ambient temperature
  3. waitwas continued for 4.5 h
  4. additionwere added
  5. customthe layers were separated
  6. extractionthe aqueous layer was extracted with CH2Cl2 (3×25 mL)
  7. washthe combined CH2Cl2 extracts were washed with water and brine
  8. dry with materialdried over MgSO4
  9. filtrationFiltration and concentration
  10. additionafter adding toluene (10 mL; to remove remaining pyridine as azeotrop)

出典と根拠

ORDレコード
ord-02969debcc9a42a2a722439e7c68826d
出典データセット
uspto-grants-2014_02
特許番号
US08653268B2

反応ノート

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