Pyridine → (S)-N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine

HRID 1523557ノート

反応式

HRID 1523557 の反応式
[N-:1]=[C:2]=[S:3].[Na+].N1C=CC=CC=1.CS(O[N:16]=[C:17](Cl)[C@H:18]1[CH2:22][O:21][C:20]2([CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[O:19]1)(=O)=O.[CH3:29][C:30]1[C:35]([O:36][C:37]2[C:38]([NH2:50])=[N:39][CH:40]=[C:41]([S:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=3)[CH:42]=2)=[CH:34][CH:33]=[CH:32][N:31]=1>C(#N)C>[CH3:29][C:30]1[C:35]([O:36][C:37]2[C:38]([NH:50][C:2]3[S:3][N:16]=[C:17]([C@H:18]4[CH2:22][O:21][C:20]5([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]5)[O:19]4)[N:1]=3)=[N:39][CH:40]=[C:41]([S:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=3)[CH:42]=2)=[CH:34][CH:33]=[CH:32][N:31]=1

参加物

6

反応物 4

HCID 1049PyridineHCID 10953423IsothiocyanatosodiumHCID 674857913-(2-Methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amineHCID 86644147(R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride

生成物 1

HCID 67486135(S)-N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine収率 70.3%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

To 700 mL of acetonitrile was added sodium isothiocyanate (12.5 g, 155 mmol), pyridine (25.2 ml, 309 mmol) and (R)—N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (38.4 g, 129 mmol) and the reaction heated to 60° C. for 15 minutes (white solid formed). To the mixture was added 3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amine (32 g, 103 mmol) as a solid and the reaction was stirred for 14 hours at 60° C. The reaction was cooled and concentrated in vacuo. The residue was partitioned between EtOAc and 1N NaOH. The aqueous mixture (basic, about 700 ML) was extracted twice with EtOAc (3000 mL total volume). The combined organic layers were washed with 1N NaOH (300 mL) and brine (300 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified by chromatography on about 1 kg of silica gel using 1:1 EtOAc/CH2Cl2 with 1% MeOH as eluent to afford (S)—N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (38.7 g, 72.4 mmol, 70.2% yield).

後処理

  1. custom(white solid formed)
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between EtOAc and 1N NaOH
  5. extractionThe aqueous mixture (basic, about 700 ML) was extracted twice with EtOAc (3000 mL total volume)
  6. washThe combined organic layers were washed with 1N NaOH (300 mL) and brine (300 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on about 1 kg of silica gel using 1:1 EtOAc/CH2Cl2 with 1% MeOH as eluent

出典と根拠

ORDレコード
ord-1205a05e33554ca787597ab281a1b949
出典データセット
uspto-grants-2015_07
特許番号
US09079890B2

反応ノート

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