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

HRID 1511072노트

반응식

HRID 1511072 반응식
[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:31]([S:36][C:37]2[CH:38]=[C:39]([O:44][C:45]3[C:46]([CH3:51])=[N:47][CH:48]=[CH:49][CH:50]=3)[C:40]([NH2:43])=[N:41][CH:42]=2)=[N:32][CH:33]=[CH:34][CH:35]=1>C(#N)C>[CH3:29][C:30]1[C:31]([S:36][C:37]2[CH:38]=[C:39]([O:44][C:45]3[C:46]([CH3:51])=[N:47][CH:48]=[CH:49][CH:50]=3)[C:40]([NH:43][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:41][CH:42]=2)=[N:32][CH:33]=[CH:34][CH:35]=1

참가 물질

6

반응물 4

HCID 1049PyridineHCID 10953423IsothiocyanatosodiumHCID 674860565-(3-Methylpyridin-2-ylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-amineHCID 86644147(R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride

생성물 1

HCID 68473492(S)-N-(5-(3-methylpyridin-2-ylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine수율 66.8%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
60 °C

실험 절차

To acetonitrile (50 mL) was added sodium isothiocyanate (0.1749 g, 2.158 mmol), pyridine (0.3740 ml, 4.624 mmol), followed by (R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (0.5507 g, 1.850 mmol), and the resulting mixture was heated to 60° C. for 30 minutes. 5-(3-Methylpyridin-2-ylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-amine (0.500 g, 1.541 mmol) was added and the reaction was stirred overnight at 60° C. The reaction was concentrated in vacuo and the residue was partitioned between ethyl acetate and 1N NaOH. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and concentrated. The residue was dried over silica gel (100% ethyl acetate). Concentration of the major UV active fraction with an Rf of 0.5 afforded (S)-N-(5-(3-methylpyridin-2-ylthio)-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (0.565 g, 1.030 mmol, 66.8% yield) as an off white powder/crystals.

후처리

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe residue was partitioned between ethyl acetate and 1N NaOH
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was dried over silica gel (100% ethyl acetate)

출처 및 근거

ORD 기록
ord-e20f2a90e4b9458999eaad9c4e21c87f
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08212045B2

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