Pyridine → (S)-N-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amine

HRID 1523662Notes

Reaction equation

HRID 1523662 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.[S-:19][C:20]#[N:21].[Na+].N1C=CC=CC=1.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[S:35][C:36]1[CH:37]=[C:38]([O:43][C:44]2[C:45]([CH3:51])=[N:46][N:47]([CH3:50])[C:48]=2[CH3:49])[C:39]([NH2:42])=[N:40][CH:41]=1>O.C(#N)C>[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[S:35][C:36]1[CH:37]=[C:38]([O:43][C:44]2[C:45]([CH3:51])=[N:46][N:47]([CH3:50])[C:48]=2[CH3:49])[C:39]([NH:42][C:20]2[S:19][N:6]=[C:7]([C@H:8]3[CH2:12][O:11][C:10]4([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]4)[O:9]3)[N:21]=2)=[N:40][CH:41]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 516871Sodium thiocyanateHCID 674864745-(Pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-amineHCID 86644147(R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride

Product 1

HCID 67487345(S)-N-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amineYield 54.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

A flask was charged with (R)—N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (2.32 g, 7.79 mmol), sodium thiocyanate (0.557 g, 6.87 mmol), pyridine (1.67 ml, 20.6 mmol), and acetonitrile (100 mL). The reaction was heated to 40° C. for 30 minutes, then 5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-amine (1.5 g, 4.58 mmol) was added and the reaction was heated to 70° C. overnight. Water was added and the reaction was extracted with ethyl acetate and dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified over silica gel (50-100% ethyl acetate in hexanes) to afford (S)—N-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-amine (1.38 g, 2.50 mmol, 54.6% yield) as yellow solid.

Workup

  1. temperaturethe reaction was heated to 70° C. overnight
  2. extractionthe reaction was extracted with ethyl acetate and dichloromethane
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified over silica gel (50-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-72efe06b37d944e9823be10047ab3814
Source dataset
uspto-grants-2015_07
Patent number
US09079890B2

Reaction notes

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