Pyridine → (R)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-1,2,4-thiadiazol-5-amine

HRID 1511142Notes

Reaction equation

HRID 1511142 reaction equation
[CH3:1][C:2]1([CH3:15])[O:6][C@H:5]([C:7](Cl)=[N:8]OS(C)(=O)=O)[CH2:4][O:3]1.[S-:16][C:17]#[N:18].[Na+].N1C=CC=CC=1.[CH3:26][C:27]1[C:32]([O:33][C:34]2[C:35]([NH2:47])=[N:36][CH:37]=[C:38]([S:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=3)[CH:39]=2)=[CH:31][CH:30]=[CH:29][N:28]=1>O.C(OCC)(=O)C>[CH3:15][C:2]1([CH3:1])[O:6][C@H:5]([C:7]2[N:18]=[C:17]([NH:47][C:35]3[C:34]([O:33][C:32]4[C:27]([CH3:26])=[N:28][CH:29]=[CH:30][CH:31]=4)=[CH:39][C:38]([S:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=4)=[CH:37][N:36]=3)[S:16][N:8]=2)[CH2:4][O:3]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 516871Sodium thiocyanateHCID 674857913-(2-Methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amineHCID 86644161(S)-2,2-dimethyl-N-(methylsulfonyloxy)-1,3-dioxolane-4-carbimidoyl chloride

Product 1

HCID 68477969(R)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-1,2,4-thiadiazol-5-amineYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A flask was charged with (S)-2,2-dimethyl-N-(methylsulfonyloxy)-1,3-dioxolane-4-carbimidoyl chloride (4.5 g, 18 mmol), sodium thiocyanate (1.3 g, 15 mmol), pyridine (3.8 ml, 46 mmol), and ethyl acetate (200 mL). The reaction was stirred and heated at 40° C. for 45 minutes. 3-(2-Methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amine (3.2 g, 10 mmol) was added and the reaction was stirred at 70° C. overnight. Water was added and the reaction was extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated. The residue was purified over silica gel (25 to 100% ethyl acetate in hexanes) to afford (R)-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-1,2,4-thiadiazol-5-amine (3.8 g, 7.7 mmol, 75% yield).

Workup

  1. stirringthe reaction was stirred at 70° C. overnight
  2. extractionthe reaction was extracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified over silica gel (25 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f7be8551973b447b88b5c08da3235ca5
Source dataset
uspto-grants-2012_07
Patent number
US08212045B2

Reaction notes

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