Ammonia → US11401286, Example 139

HRID 1508809ノート

反応式

HRID 1508809 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22](OCC)=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH:27]3[CH2:29][CH2:28]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.O1CCOCC1.[NH3:36]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH2:36])=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH:27]3[CH2:28][CH2:29]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 222AmmoniaHCID 312751,4-DioxaneHCID 90112160HCID 90112160、化合物

生成物 1

HCID 90111592US11401286, Example 139収率 27.6%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
100 °C

実験手順

A 20-mL vial was charged with ethyl 2-(4-((2-(3-chlorophenyl)-6-cyclopropylpyridin-4-yl)amino)phenyl)acetate (0.090 g, 0.23 mmol), dioxane (1 mL) and methanol (3 mL). To this solution was added NH3 (6.0 mL, 7N in methanol, 42.0 mmol). The vial was sealed and the resulting mixture was stirred at 100° C. for 47 h. The crude reaction mixture was concentrated under reduced pressure. The residue was adsorbed onto silica then purified by chromatography on silica using hexanes/ethyl acetate (10:0 to 0:10) as eluent followed by chromatography on silica using dichloromethane/methanol (10:0 to 9:1) as eluent to afford 2-(4-((2-(3-chlorophenyl)-6-cyclopropylpyridin-4-yl)amino)phenyl)acetamide (0.024 g, 27%) as a colorless oil. MW=377.87. 1H NMR (CDCl3, 500 MHz) δ 7.94-7.91 (m, 1H), 7.81-7.76 (m, 1H), 7.36-7.31 (m, 2H), 7.30-7.26 (m, 2H), 7.21-7.17 (m, 2H), 7.01 (d, J=2.0 Hz, 1H), 6.68 (d, J=2.5 Hz, 1H), 6.02 (s, 1H), 5.45 (br s, 2H), 3.58 (s, 2H), 1.99-1.93 (m, 1H), 1.13-1.08 (m, 2H), 0.97-0.92 (m, 2H); ESI MS m/z 378 [M+H]+. Treatment with 1.25M HCl (0.103 mL, 0.130 mol) in methanol afforded the title compound (0.022 g, 84%) as an off-white solid. MW=414.33. M.p. 104-106° C. 1H NMR (DMSO-d6, 500 MHz) δ 13.48 (br s, 1H), 8.78 (br s, 1H), 7.92 (d, J=1.0 Hz, 1H), 7.84-7.76 (m, 1H), 7.52 (br s, 2H), 7.45 (s, 1H), 7.30-7.25 (m, 2H), 7.25-7.16 (m, 2H), 7.11 (s, 1H), 6.87 (s, 1H), 6.74 (s, 1H), 3.36 (s, 2H), 2.15-2.02 (m, 1H), 1.10-0.90 (m, 4H); ESI MS m/z 378 [M+H]+.

後処理

  1. customThe vial was sealed
  2. customThe crude reaction mixture
  3. concentrationwas concentrated under reduced pressure
  4. customthen purified by chromatography on silica

出典と根拠

ORDレコード
ord-98331ad26ce14f20ac4d7bea44b99446
出典データセット
uspto-grants-2015_12
特許番号
US09221843B2

反応ノート

読み込み中…