Pyridine → (S)-N-(3-(2,4-dimethylpyridin-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 1511079Notes

Reaction equation

HRID 1511079 reaction equation
[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)=[C:34]([CH3:51])[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)=[C:34]([CH3:51])[CH:33]=[CH:32][N:31]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 10953423IsothiocyanatosodiumHCID 674875013-(2,4-Dimethylpyridin-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 67487138(S)-N-(3-(2,4-dimethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amineYield 50.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To acetonitrile (50 mL) was added sodium isothiocyanate (0.1469 g, 1.813 mmol), pyridine (0.3141 ml, 3.884 mmol), followed by (R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (0.4626 g, 1.554 mmol) and the resulting mixture was heated to 60° C. for 30 minutes. 3-(2,4-Dimethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amine (0.500 g, 1.295 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 purified over silica gel (100% ethyl acetate). Concentration of the major UV component with an Rf of 0.5 afforded (S)-N-(3-(2,4-dimethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (0.360 g, 0.6561 mmol, 50.7% yield) as a light yellow powder.

Workup

  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 purified over silica gel (100% ethyl acetate)

Sources & evidence

ORD record
ord-4a775dc0813a4ea4b127a411697aa01f
Source dataset
uspto-grants-2012_07
Patent number
US08212045B2

Reaction notes

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