Acetic Anhydride → 1-(4-(5-(3-(2-Methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanone

HRID 1809653Notes

Reaction equation

HRID 1809653 reaction equation
[CH3:1][C:2]1[C:7]([O:8][C:9]2[C:10]([NH:22][C:23]3[S:27][N:26]=[C:25]([CH:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)[N:24]=3)=[N:11][CH:12]=[C:13]([S:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH:14]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[C:41](OC(=O)C)(=[O:43])[CH3:42].C(=O)(O)[O-].[Na+]>C1COCC1.O>[CH3:1][C:2]1[C:7]([O:8][C:9]2[C:10]([NH:22][C:23]3[S:27][N:26]=[C:25]([CH:28]4[CH2:33][CH2:32][N:31]([C:41](=[O:43])[CH3:42])[CH2:30][CH2:29]4)[N:24]=3)=[N:11][CH:12]=[C:13]([S:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH:14]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 67487355N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(piperidin-4-yl)-1,2,4-thiadiazol-5-amine

Product 1

HCID 592916411-(4-(5-(3-(2-Methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanoneYield 83.13%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(piperidin-4-yl)-1,2,4-thiadiazol-5-amine (29.52 g, 61.81 mmol) and triethylamine (21.54 ml, 154.5 mmol) were dissolved in THF (300 mL). Acetic anhydride (6.310 g, 61.81 mmol) was added and the reaction was stirred for 90 minutes. Saturated sodium bicarbonate (200 mL) and water (400 mL) were added and the reaction mixture was extracted with dichloromethane and 10% methanol in dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was dissolved in MeOH (˜75 mL) and let stand. The resultant solids were filtered and washed with cold methanol to give a first crop (22.3 g). The filtrate was concentrated and solids were redissolved in methanol (30 mL) and allowed to stand. The precipitated solids were filtered and washed to afford a second crop (4.3 g). The 2 crops were combined to afford 1-(4-(5-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)ethanone (26.7 g, 51.38 mmol, 83.13% yield).

Workup

  1. extractionthe reaction mixture was extracted with dichloromethane and 10% methanol in dichloromethane
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in MeOH (˜75 mL)
  6. filtrationThe resultant solids were filtered
  7. washwashed with cold methanol
  8. customto give a first crop (22.3 g)
  9. concentrationThe filtrate was concentrated
  10. dissolutionsolids were redissolved in methanol (30 mL)
  11. filtrationThe precipitated solids were filtered
  12. washwashed
  13. customto afford a second crop (4.3 g)

Sources & evidence

ORD record
ord-c626aaf51dec488f84948ce40658c974
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

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