Pyridine → (S)-N-(3-(2-ethylpyridin-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 1511046Notes

Reaction equation

HRID 1511046 reaction equation
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.N1C=CC=CC=1.[S-:25][C:26]#[N:27].[Na+].[CH2:29]([C:31]1[C:36]([O:37][C:38]2[C:39]([NH2:51])=[N:40][CH:41]=[C:42]([S:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][N:46]=3)[CH:43]=2)=[CH:35][CH:34]=[CH:33][N:32]=1)[CH3:30]>C(#N)C>[CH2:29]([C:31]1[C:36]([O:37][C:38]2[C:39]([NH:51][C:26]3[S:25][N:6]=[C:7]([C@H:8]4[CH2:12][O:11][C:10]5([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]5)[O:9]4)[N:27]=3)=[N:40][CH:41]=[C:42]([S:44][C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][N:46]=3)[CH:43]=2)=[CH:35][CH:34]=[CH:33][N:32]=1)[CH3:30]

Participants

6

Reactant 4

HCID 1049PyridineHCID 516871Sodium thiocyanateHCID 674859303-(2-Ethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amineHCID 86644147(R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride

Product 1

HCID 68478697(S)-N-(3-(2-ethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amineYield 57.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

(R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (0.854 g, 2.87 mmol), pyridine (0.618 ml, 7.64 mmol), and sodium thiocyanate (0.310 g, 3.82 mmol) were dissolved in acetonitrile (10 mL). The solution was heated to 60° C. for 30 minutes. 3-(2-ethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amine (0.620 g, 1.91 mmol) was added and the reaction was heated at 60° C. overnight. The solution was quenched with saturated aqueous NaHCO3 solution, extracted with EtOAc (3×100 mL), washed with brine, dried over MgSO4, and concentrated. The material was purified over silica gel (25 to 100% ethyl acetate in hexanes) to afford (S)-N-(3-(2-ethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (0.600 g, 1.09 mmol).

Workup

  1. temperaturethe reaction was heated at 60° C. overnight
  2. customThe solution was quenched with saturated aqueous NaHCO3 solution
  3. extractionextracted with EtOAc (3×100 mL)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe material was purified over silica gel (25 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-855f0adf4c0949e0b09739d2a174b10d
Source dataset
uspto-grants-2012_07
Patent number
US08212045B2

Reaction notes

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