Ammonia → HCID 90113020、化合物

HRID 1508814ノート

反応式

HRID 1508814 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22](O)=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([C:25]([F:28])([F:27])[F:26])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[NH3:35].CO>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH2:35])=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([C:25]([F:27])([F:26])[F:28])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 222AmmoniaHCID 887MethanolHCID 65578Oxalyl chlorideHCID 90111638Zatolmilast

生成物 1

HCID 90113020HCID 90113020、化合物収率 21%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

An 100-mL round bottom flask was charged with 2-(4-((2-(3-chlorophenyl)-6-(trifluoromethyl)pyridin-4-yl)methyl)phenyl)acetic acid (0.17 g, 0.42 mmol) in dichloromethane (10 ml). To this solution at 0° C. was added oxalyl chloride (0.18 mL, 2.10 mmol) followed by DMF (1 drop). After stirring for 5 h the volatile material was removed under reduced pressure to afford crude acid chloride. The residue was dissolved in dichloromethane (10 mL), cooled to 0° C., and 7N ammonia in methanol (10.0 mL, 70 mmol) was added. After stirring for 0.5 h, the volatile material was removed under reduced pressure. The residue was 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 the title compound (0.079 g, 21%) as an off-white solid. MW=404.81. M.p. 148-160° C. 1H NMR (DMSO-d6, 500 MHz) δ 8.33 (s, 1H), 8.17-8.15 (m, 1H), 8.11-8.05 (m, 1H), 7.76 (d, J=0.5 Hz, 1H), 7.60-7.55 (m, 2H), 7.41 (br s, 1H), 7.31 (d, J=8.0 Hz, 2H), 7.21 (d, J=8.0 Hz, 2H), 6.82 (br s, 1H), 4.11 (s, 2H), 3.32 (s, 2H); APCI MS m/z 405 [M+H]+.

後処理

  1. customwas removed under reduced pressure
  2. customto afford crude acid chloride
  3. stirringAfter stirring for 0.5 h
  4. customthe volatile material was removed under reduced pressure
  5. customThe residue was purified by chromatography on silica

出典と根拠

ORDレコード
ord-311fbe2e208e4ad4994978db81af1ce8
出典データセット
uspto-grants-2015_12
特許番号
US09221843B2

反応ノート

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