Trifluoroacetic acid → N-(6-(4-(5-amino-1,3,4-thiadiazol-2-yl)butyl)pyridazin-3-yl)-2-phenylacetamide

HRID 538094Notes

Reaction equation

HRID 538094 reaction equation
[C:1]([CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[N:12]=[N:11][C:10]([NH:13][C:14](=[O:22])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:9][CH:8]=1)#[N:2].N[NH:24][C:25]([NH2:27])=[S:26].FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>O>[NH2:27][C:25]1[S:26][C:1]([CH2:3][CH2:4][CH2:5][CH2:6][C:7]2[N:12]=[N:11][C:10]([NH:13][C:14](=[O:22])[CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:9][CH:8]=2)=[N:2][N:24]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 2723789ThiosemicarbazideHCID 86687868N-(6-(4-cyanobutyl)pyridazin-3-yl)-2-phenylacetamide

Product 1

HCID 74982601N-(6-(4-(5-amino-1,3,4-thiadiazol-2-yl)butyl)pyridazin-3-yl)-2-phenylacetamideYield 81.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

N-(6-(4-cyanobutyl)pyridazin-3-yl)-2-phenylacetamide (14.7 g, 50.2 mmol) was charged into a 250 mL round bottom flask fitted with an open top reflux condenser. To the flask was added thiosemicarbazide (5.03 g, 55.2 mmol) and trifluoroacetic acid (88 mL). The reaction slurry was heated in a 65° C. bath for 2 h. After cooling to RT, H2O (150 mL) was added and stirred for 30 minutes. The mixture was then slowly transferred to a stirred 7.5% sodium bicarbonate solution (1400 mL) cooled in a 0° C. bath. The precipitate was collected by suction filtration, rinsed with water (2×200 mL), diethyl ether (2×200 mL) and dried under high vacuum overnight. The off-white solid was slurried in DMSO (200 mL) and heated in an 80° C. bath until the internal temperature reached 65° C. DMSO (105 mL) was used to rinse sides of flask. H2O (120 mL) was slowly added until the solution became slightly cloudy and then the mixture was removed from heat bath and allowed to cool to ambient temperature while stirring. The pale green precipitate was collected by suction filtration, rinsed with water (200 mL) and diethyl ether (2×200 mL). The solid was dried overnight under high vacuum to provide N-(6-(4-(5-amino-1,3,4-thiadiazol-2-yl)butyl)pyridazin-3-yl)-2-phenylacetamide (1024, 15.01 g). 1H NMR (300 MHz, DMSO-d6) δ 11.28 (s, 1H), 8.23 (d, J=8.916 Hz, 1H), 7.59 (d, J=8.826 Hz, 1H), 7.36 (m, 5H), 7.07 (s, 2H), 3.78 (s, 2H), 2.87 (t, J=6.799 Hz, 4H), 1.69 (bm, 4H)

Workup

  1. customfitted with an open top
  2. temperaturereflux condenser
  3. temperatureAfter cooling to RT
  4. temperaturecooled in a 0° C. bath
  5. filtrationThe precipitate was collected by suction filtration
  6. washrinsed with water (2×200 mL), diethyl ether (2×200 mL)
  7. customdried under high vacuum overnight
  8. temperatureheated in an 80° C. bath until the internal temperature
  9. customreached 65° C
  10. washto rinse sides of flask
  11. additionH2O (120 mL) was slowly added until the solution
  12. customthe mixture was removed
  13. temperaturefrom heat bath
  14. temperatureto cool to ambient temperature
  15. stirringwhile stirring
  16. filtrationThe pale green precipitate was collected by suction filtration
  17. washrinsed with water (200 mL) and diethyl ether (2×200 mL)
  18. customThe solid was dried overnight under high vacuum

Sources & evidence

ORD record
ord-eaa2c360f0344f47b9713ea7e35dba66
Source dataset
uspto-grants-2014_10
Patent number
US08865718B2

Reaction notes

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