Trifluoromethanesulfonic acid → 1-(5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone

HRID 1812217ノート

反応式

HRID 1812217 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[CH:17]=[C:18]([C:32](=[O:34])[CH3:33])[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=3)[N:10]=2)=CC=1.S(O)(C(F)(F)F)(=O)=O>C(O)(C(F)(F)F)=O>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[CH:17]=[C:18]([C:32](=[O:34])[CH3:33])[CH:19]=[N:20][C:21]=2[NH:22][C:23]2[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=2)[N:10]=1

参加物

4

反応物 2

HCID 62406Trifluoromethanesulfonic acidHCID 666002411-(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)ethanone

生成物 1

HCID 665998701-(5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone収率 70.2%

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

反応条件

温度
80 °C

実験手順

A solution of 1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (Example 271; 332 mg, 0.54 mmol) in TFA (3 mL) was treated with TfOH (0.1 mL). The solution was heated at 80° C. in an oil bath for 4 h, allowed to cool to room temperature, and concentrated. The dark residue was treated with a few ice cubes followed by sat. NaHCO3 while rapidly stirring. The precipitated yellow solid was collected by filtration and rinsed with water (5 mL). The yellow solid was purified by flash chromatography eluting with 1-15% MeOH in DCM to give 1-(5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (140 mg, 69%) as a bright yellow crystalline solid. m/z (ESI, +ve ion) 460 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.38 (br., 1H); 9.26 (d, J=2.2 Hz, 1H); 8.96 (d, J=2.2 Hz, 1H); 8.42 (s, 1H); 8.35 (dd, J=12.3, 1.6 Hz, 1H); 8.00 (s, 1H); 7.83 (s, 1H); 3.96 (s, 3H); 2.57 (s, 3H); 2.46 (s, 3H).

後処理

  1. temperatureto cool to room temperature
  2. concentrationconcentrated
  3. additionThe dark residue was treated with a few ice cubes
  4. filtrationThe precipitated yellow solid was collected by filtration
  5. washrinsed with water (5 mL)
  6. customThe yellow solid was purified by flash chromatography
  7. washeluting with 1-15% MeOH in DCM

出典と根拠

ORDレコード
ord-37c5fe81bf0e4075a83bd6bb40921bd4
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

反応ノート

読み込み中…