N-(3-aminobenzyl)-2,2,2-trifluoroacetamide → 2,2,2-Trifluoro-N-[(3-{[4-(2-{3-[(3-thienylacetyl)amino]phenyl}pyrazolo-[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}phenyl)methyl]acetamide

HRID 1157595ノート

反応式

HRID 1157595 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1.Cl[C:17]1[N:22]=[C:21]([C:23]2[C:24]([C:32]3[CH:33]=[C:34]([NH:38][C:39](=[O:46])[CH2:40][C:41]4[CH:45]=[CH:44][S:43][CH:42]=4)[CH:35]=[CH:36][CH:37]=3)=[N:25][N:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=23)[CH:20]=[CH:19][N:18]=1>CC(O)C.Cl.C(Cl)Cl>[F:14][C:11]([F:12])([F:13])[C:10]([NH:9][CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:17]2[N:22]=[C:21]([C:23]3[C:24]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([NH:38][C:39](=[O:46])[CH2:40][C:41]5[CH:45]=[CH:44][S:43][CH:42]=5)[CH:33]=4)=[N:25][N:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=34)[CH:20]=[CH:19][N:18]=2)[CH:3]=1)=[O:15]

参加物

6

反応物 2

HCID 21131928N-(3-aminobenzyl)-2,2,2-trifluoroacetamideHCID 57737204N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(3-thienyl)acetamide

生成物 1

HCID 577372022,2,2-Trifluoro-N-[(3-{[4-(2-{3-[(3-thienylacetyl)amino]phenyl}pyrazolo-[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}phenyl)methyl]acetamide収率 53%

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid触媒HCID 3776Isopropanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
80 °C

実験手順

A suspension of N-[(3-aminophenyl)methyl]-2,2,2-trifluoroacetamide (73 mg, 0.34 mmol) and N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(3-thienyl)acetamide (120 mg, 0.27 mmol) in i-PrOH (4 mL) was acidified with 3 drops of 12 N HCl and stirred at 80° C. overnight. After 16 h, the reaction mixture was diluted with DCM, washed with saturated aqueous NaHCO3, dried over Na2SO4, and adsorbed onto silica gel. The crude product was purified by column chromatography to generate the title compound in 53% yield. 1H NMR (400 MHz, d6-DMSO) δ 10.28 (s, 1H), 9.98 (t, 1H), 9.63 (s, 1H), 8.83 (d, J=6.9 Hz, 1H), 8.52 (d, J=9.0 Hz, 1H), 8.24 (d, J=5.1 Hz, 1H), 7.90 (s, 1H), 7.63 (s, 1H), 7.75 (d, J=9.0 Hz, 1H), 7.71 (s, 1H), 7.67 (d, J=8.2 Hz, 1H), 7.47-7.49 (m, 2H), 7.42 (t, J=7.9 Hz, 1H), 7.32 (d, J=2.2 Hz, 1H), 7.26 (d, J=9.1 Hz, 1H), 7.22 (d, J=7.9 Hz, 1H), 7.08-7.13 (m, 2H), 6.85 (d, J=7.7 Hz, 1H), 6.51 (d, J=5.1 Hz, 1H), 4.35 (d, J=5.9 Hz, 2H), 3.66 (s, 2H). ES-LC/MS m/z=628 [M+H]+.

後処理

  1. waitAfter 16 h
  2. washwashed with saturated aqueous NaHCO3
  3. dry with materialdried over Na2SO4
  4. customThe crude product was purified by column chromatography

出典と根拠

ORDレコード
ord-87c15a6c145941778144e3f26a02e154
出典データセット
uspto-grants-2010_10
特許番号
US07807673B2

反応ノート

読み込み中…