Stannous chloride dihydrate → 4-[5-(Acetylamino)pyridin-2-yl]piperazin-1-yl-5-(4-fluoro phenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine

HRID 72680

反応式

HRID 72680 の反応式
Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[C:6]([C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[N:5]=[C:4]([C:25]([F:28])([F:27])[F:26])[N:3]=1.[N+:29]([C:32]1[CH:33]=[CH:34][C:35]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[N:36][CH:37]=1)([O-])=O.C(N([CH:50]([CH3:52])C)CC)(C)C.[OH2:53].O.[Sn](Cl)Cl>C(O)(=O)C.C(#N)C>[C:50]([NH:29][C:32]1[CH:33]=[CH:34][C:35]([N:38]2[CH2:43][CH2:42][N:41]([C:2]3[C:7]([C:8]4[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=4)=[C:6]([C:15]4[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:22])=[O:23])=[CH:17][CH:16]=4)[N:5]=[C:4]([C:25]([F:27])([F:28])[F:26])[N:3]=3)[CH2:40][CH2:39]2)=[N:36][CH:37]=1)(=[O:53])[CH3:52]

参加物

7

反応物 4

HCID 61436Stannous chloride dihydrateHCID 81531DiisopropylethylamineHCID 29287991-(5-Nitropyridin-2-yl)piperazineHCID 99105864-Chloro-5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoro methyl)pyrimidine

生成物 1

HCID 250043724-[5-(Acetylamino)pyridin-2-yl]piperazin-1-yl-5-(4-fluoro phenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoromethyl)pyrimidine

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
62.5 °C

実験手順

4-Chloro-5-(4-fluorophenyl)-6-[4-(methylsulfonyl)phenyl]-2-(trifluoro methyl)pyrimidine (0.15 g, 0.35 mmol) was treated with 1-(5-nitropyridin-2-yl)piperazine (0.087 g, 0.418 mmol) and diisopropylethylamine (0.06 mL, 0.35 mmol), acetonitrile (2.5 ml) and the reaction mixture was heated at 60-65° C. for 2 hours. Subsequently the reaction mixture was precipitated by the addition of diisopropyl ether (2 ml). The above-obtained solid (0.11 g, 0.182 mmol) was taken up in acetic acid (2 ml) and tin (II) chloride dihydrate (0.123 g, 0.182 mmol) was added to it. Stirring was continued further for 11 hours and then the reaction mixture was poured onto ice-cold water and extracted with ethyl acetate (2×25 ml). After neutralization with sodium bicarbonate, the organic layer was evaporated to obtain the crude material, which was purified by column chromatography (2% MeOH in dichloromethane) to yield the title compound. 1H-NMR (DMSO-d6) δ: 1.99 (s, 3H), 3.19 (s, 3H), 3.29-3.40 (m, 8H), 6.77 (d, 1H), 7.19-7.23 (m, 2H), 7.31-7.34 (m, 2H), 7.36 (d, 2H), 7.74 (d, 1H), 7.80 (d, 2H), 8.24 (d, 1H), 9.77 (s, 1H, D2O exchangeable); MS m/z: 615.1 (M++1).

後処理

  1. customSubsequently the reaction mixture was precipitated by the addition of diisopropyl ether (2 ml)
  2. additionthe reaction mixture was poured onto ice-cold water
  3. extractionextracted with ethyl acetate (2×25 ml)
  4. customAfter neutralization with sodium bicarbonate, the organic layer was evaporated
  5. customto obtain the crude material, which
  6. customwas purified by column chromatography (2% MeOH in dichloromethane)

出典と根拠

ORDレコード
ord-317c833ae9cd42059a202cede178102d
出典データセット
uspto-grants-2014_09
特許番号
US08828999B2

関連ノート

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