Dichloromethane → 4-Phenyl-1-{[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-7-yl]methyl}pyrrolidin-2-one

HRID 1924328Notes

Reaction equation

HRID 1924328 reaction equation
Cl.[NH2:2][CH2:3][CH:4]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:5][C:6]([O:8]C)=O.[F:16][C:17]([F:30])([F:29])[C:18]1[N:22]2[N:23]=[CH:24][C:25]([CH:27]=O)=[CH:26][C:21]2=[N:20][N:19]=1.C(N(CC)CC)C.ClCCl>ClC(Cl)C.COCCOC>[C:10]1([CH:4]2[CH2:3][N:2]([CH2:27][C:25]3[CH:24]=[N:23][N:22]4[C:18]([C:17]([F:30])([F:16])[F:29])=[N:19][N:20]=[C:21]4[CH:26]=3)[C:6](=[O:8])[CH2:5]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 536292043-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine-7-carbaldehydeHCID 68748102Methyl 4-amino-3-phenylbutanoate hydrochloride

Product 1

HCID 577430604-Phenyl-1-{[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-7-yl]methyl}pyrrolidin-2-oneYield 36%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
11 °C

Procedure

Methyl 4-amino-3-phenylbutanoate hydrochloride x11 (0.19 g, 0.83 mmol, 1.05 eq) is added to a solution of aldehyde x235 (0.17 g, 0.79 mmol) in dry dichloroethane (DCE) (7.8 ml). The mixture is kept at room temperature for 30 min, cooled to 10-12° C., and a solution of triethylamine (0.15 ml, 0.83 mmol, 1.05 eq) in dry DME (2.5 ml) is added dropwise. The mixture is additionally stirred at the same temperature for 1 h and cooled to 0-5° C. Then STAB (0.23 g, 1.10 mmol, 1.4 eq) is added in portions under vigorous stirring. The mixture is additionally stirred at 0-5° C. for 30 min and kept at room temperature overnight. Then the mixture is heated to 60° C. for 2 h and cooled to room temperature. An equal volume of dichloromethane is added, and the mixture is washed with 10% K2CO3 (2×10 ml). The mixture is dried over anhydrous Na2SO4 and evaporated. The oily residue is triturated with ether, and the formed crystals are separated by filtration, washed twice with ether, and vacuum-dried to give white fine-crystalline 4-phenyl-1-{[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-7-yl]methyl}pyrrolidin-2-one 255.

Workup

  1. temperaturecooled to 0-5° C
  2. additionThen STAB (0.23 g, 1.10 mmol, 1.4 eq) is added in portions under vigorous stirring
  3. stirringThe mixture is additionally stirred at 0-5° C. for 30 min
  4. waitkept at room temperature overnight
  5. temperatureThen the mixture is heated to 60° C. for 2 h
  6. temperaturecooled to room temperature
  7. washthe mixture is washed with 10% K2CO3 (2×10 ml)
  8. dry with materialThe mixture is dried over anhydrous Na2SO4
  9. customevaporated
  10. customThe oily residue is triturated with ether
  11. customthe formed crystals are separated by filtration
  12. washwashed twice with ether
  13. customvacuum-dried

Sources & evidence

ORD record
ord-98c830fd011c4dbd8aae50cfce0566de
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

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