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 1511125노트

반응식

HRID 1511125 반응식
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

참가 물질

7

반응물 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

생성물 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-amine수율 54.6%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

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온도
40 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-96e019db245242c8bbd85c8d8acb3167
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08212045B2

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