Trifluoroacetic acid → N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(piperidin-4-yl)-1,2,4-thiadiazol-5-amine

HRID 1809652Notes

Reaction equation

HRID 1809652 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][N:31](C(OC(C)(C)C)=O)[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(O)(C(F)(F)F)=O>C(Cl)Cl>[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

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 68708604Tert-butyl 4-(5-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate

Product 1

HCID 67487355N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(piperidin-4-yl)-1,2,4-thiadiazol-5-amineYield 94.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl 4-(5-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidine-1-carboxylate (38.10 g, 65.95 mmol) was dissolved in CH2Cl2 (500 mL) and cooled to 0° C. TFA (25.40 ml, 329.7 mmol) was added over 5 minutes, keeping the internal temperature below 12° C. The reaction was then warmed to ambient temperature and stirred for 1 hour. More TFA (75 mL, 990 mmol) was added and the reaction was stirred for 2 hours. The reaction was concentrated and redissolved in 10% methanol in dichloromethane (450 mL) and saturated sodium bicarbonate was slowly added. The mixture was stirred for 1 hour and filtered. The solids were washed with water and dried in a vacuum oven to give N-(3-(2-methylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(piperidin-4-yl)-1,2,4-thiadiazol-5-amine (29.7 g, 62.19 mmol, 94.29% yield).

Workup

  1. customthe internal temperature below 12° C
  2. temperatureThe reaction was then warmed to ambient temperature
  3. stirringthe reaction was stirred for 2 hours
  4. concentrationThe reaction was concentrated
  5. dissolutionredissolved in 10% methanol in dichloromethane (450 mL)
  6. additionsaturated sodium bicarbonate was slowly added
  7. stirringThe mixture was stirred for 1 hour
  8. filtrationfiltered
  9. washThe solids were washed with water
  10. customdried in a vacuum oven

Sources & evidence

ORD record
ord-3d738b293ed44d889b5fcaefb759968d
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

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