Trifluoroacetic acid → (R)-N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine

HRID 1621842ノート

反応式

HRID 1621842 の反応式
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:34][C:35]4[CH:44]=[C:43]5[C:38]([CH:39]=[CH:40][CH:41]=[N:42]5)=[C:37]([F:45])[CH:36]=4)=[N:18][CH:19]=[C:20]([C@H:22]([N:24]4[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:26][CH2:25]4)[CH3:23])[CH:21]=3)[N:10]=2)=CC=1.FC(F)(F)C(O)=O>>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[C:17]([NH:34][C:35]3[CH:44]=[C:43]4[C:38]([CH:39]=[CH:40][CH:41]=[N:42]4)=[C:37]([F:45])[CH:36]=3)=[N:18][CH:19]=[C:20]([C@H:22]([N:24]3[CH2:25][CH2:26][N:27]([S:30]([CH3:33])(=[O:31])=[O:32])[CH2:28][CH2:29]3)[CH3:23])[CH:21]=2)[N:10]=1

参加物

3

反応物 2

HCID 6422Trifluoroacetic acidHCID 66611412HCID 66611412、化合物

生成物 1

HCID 59548193(R)-N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine収率 58.2%

反応条件

温度
75 °C

実験手順

A glass microwave reaction vessel was charged with (R)—N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine (82 mg, 0.105 mmol) and trifluoroacetic acid (1 mL, 13.46 mmol, Aldrich). The reaction mixture was stirred and heated in an oil bath at 75° C. for 14 h. The solvent was removed in vacuo. The residue was treated with 10% MeOH/CH2Cl2 (40 mL). The reaction mixture was washed with sat. NaHCO3 (10 mL), saturated NaCl (10 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow solid. The crude product was purified by silica gel chromatography eluting with 5% MeOH/CH2Cl2 to give (R)—N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)-5-fluoroquinolin-7-amine (33 mg, 0.061 mmol, 58.2% yield). 1H NMR (300 MHz, CDCl3) δ 1.47 (d, J=6.72 Hz, 3H) 2.52-2.72 (m, 7H) 2.78 (s, 3H) 3.25 (t, J=4.17 Hz, 4H) 3.60 (q, J=6.53 Hz, 1H) 5.49 (s, 2H) 7.12-7.24 (m, 1H) 7.39-7.54 (m, 1H) 7.83 (d, J=8.33 Hz, 1H) 8.48 (d, J=2.19 Hz, 1H) 8.77 (d, J=2.05 Hz, 1H) 8.96 (d, J=2.34 Hz, 1H) 9.25 (d, J=1.90 Hz, 1H) 12.51 (s, 1H). m/z (ESI, +ve ion) 538.1 (M+H)+.

後処理

  1. customA glass microwave reaction vessel
  2. customThe solvent was removed in vacuo
  3. additionThe residue was treated with 10% MeOH/CH2Cl2 (40 mL)
  4. washThe reaction mixture was washed with sat. NaHCO3 (10 mL), saturated NaCl (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto give the crude material as a yellow solid
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 5% MeOH/CH2Cl2

出典と根拠

ORDレコード
ord-cc3d5152ff7a43b3bdfd9d7d07bbd790
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

読み込み中…