Pyridine → (S)-N-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amine

HRID 1523662ノート

反応式

HRID 1523662 の反応式
CS(O[N:6]=[C:7](Cl)[C@H:8]1[CH2:12][O:11][C:10]2([CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[O:9]1)(=O)=O.[S-:19][C:20]#[N:21].[Na+].N1C=CC=CC=1.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[S:35][C:36]1[CH:37]=[C:38]([O:43][C:44]2[C:45]([CH3:51])=[N:46][N:47]([CH3:50])[C:48]=2[CH3:49])[C:39]([NH2:42])=[N:40][CH:41]=1>O.C(#N)C>[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[S:35][C:36]1[CH:37]=[C:38]([O:43][C:44]2[C:45]([CH3:51])=[N:46][N:47]([CH3:50])[C:48]=2[CH3:49])[C:39]([NH:42][C:20]2[S:19][N:6]=[C:7]([C@H:8]3[CH2:12][O:11][C:10]4([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]4)[O:9]3)[N:21]=2)=[N:40][CH:41]=1

参加物

7

反応物 4

HCID 1049PyridineHCID 516871Sodium thiocyanateHCID 674864745-(Pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-amineHCID 86644147(R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride

生成物 1

HCID 67487345(S)-N-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amine収率 54.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
40 °C

実験手順

A flask was charged with (R)—N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (2.32 g, 7.79 mmol), sodium thiocyanate (0.557 g, 6.87 mmol), pyridine (1.67 ml, 20.6 mmol), and acetonitrile (100 mL). The reaction was heated to 40° C. for 30 minutes, then 5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-amine (1.5 g, 4.58 mmol) was added and the reaction was heated to 70° C. overnight. Water was added and the reaction was extracted with ethyl acetate and dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified over silica gel (50-100% ethyl acetate in hexanes) to afford (S)—N-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (1.38 g, 2.50 mmol, 54.6% yield) as yellow solid.

後処理

  1. temperaturethe reaction was heated to 70° C. overnight
  2. extractionthe reaction was extracted with ethyl acetate and dichloromethane
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified over silica gel (50-100% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-72efe06b37d944e9823be10047ab3814
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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