Pyridine → (S)-N-(3-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(2,2,5,5-tetramethyl-1,3-dioxolan-4-yl)-1,2,4-thiadiazol-5-amine

HRID 1523602Notes

Reaction equation

HRID 1523602 reaction equation
[N-:1]=[C:2]=[S:3].[Na+].N1C=CC=CC=1.[CH3:11][C:12]1([CH3:27])[O:16][C@@H:15]([C:17](Cl)=[N:18]OS(C)(=O)=O)[C:14]([CH3:26])([CH3:25])[O:13]1.[CH2:28]([N:30]1[C:34]([O:35][C:36]2[C:37]([NH2:49])=[N:38][CH:39]=[C:40]([S:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=3)[CH:41]=2)=[CH:33][CH:32]=[N:31]1)[CH3:29]>CCOC(C)=O.[OH-].[Na+]>[CH2:28]([N:30]1[C:34]([O:35][C:36]2[C:37]([NH:49][C:2]3[S:3][N:18]=[C:17]([C@H:15]4[C:14]([CH3:25])([CH3:26])[O:13][C:12]([CH3:11])([CH3:27])[O:16]4)[N:1]=3)=[N:38][CH:39]=[C:40]([S:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][N:44]=3)[CH:41]=2)=[CH:33][CH:32]=[N:31]1)[CH3:29]

Participants

7

Reactant 4

HCID 1049PyridineHCID 10953423IsothiocyanatosodiumHCID 674860483-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amineHCID 86644154(R)-2,2,5,5-tetramethyl-N-(methylsulfonyloxy)-1,3-dioxolane-4-carbimidoyl chloride

Product 1

HCID 68476855(S)-N-(3-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(2,2,5,5-tetramethyl-1,3-dioxolan-4-yl)-1,2,4-thiadiazol-5-amineYield 32%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
60 °C

Procedure

To 30 mL of EtOAc was added sodium isothiocyanate (0.0970 g, 1.20 mmol), pyridine (0.195 ml, 2.39 mmol) and (R)-2,2,5,5-tetramethyl-N-(methylsulfonyloxy)-1,3-dioxolane-4-carbimidoyl chloride (0.342 g, 1.20 mmol). The reaction was heated to 60° C. for 15 minutes. To the mixture was added 3-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amine (0.250 g, 0.798 mmol) and the reaction was stirred overnight at 70° C. The reaction was cooled and diluted with 50 ml EtOAc and 50 ml 1N NaOH. The aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated in-vacuo. The residue was purified over silica gel (50% EtOAc/Hexanes) to afford (S)—N-(3-(1-ethyl-1H-pyrazol-5-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(2,2,5,5-tetramethyl-1,3-dioxolan-4-yl)-1,2,4-thiadiazol-5-amine (0.134 g, 0.255 mmol, 32.0% yield).

Workup

  1. temperatureThe reaction was cooled
  2. extractionThe aqueous layer was extracted with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in-vacuo
  6. customThe residue was purified over silica gel (50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-a4574630cc01473a9f763b38eeb7926d
Source dataset
uspto-grants-2015_07
Patent number
US09079890B2

Reaction notes

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