Diisopropylethylamine → Tert-butyl 4-[3-(difluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazine-1-carboxylate

HRID 1674983Notes

Reaction equation

HRID 1674983 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([F:13])[F:12])=[N:9][N:10]=2)[N:7]=1.[N:14]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:12][CH:11]([F:13])[C:8]1[N:6]2[N:7]=[C:2]([N:17]3[CH2:16][CH2:15][N:14]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18]3)[CH:3]=[CH:4][C:5]2=[N:10][N:9]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 14723856-Chloro-3-(difluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine

Product 1

HCID 67340394Tert-butyl 4-[3-(difluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 6-chloro-3-(difluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (3.07 g, 15 mmol), tert-butyl piperazine-1-carboxylate (3.35 g, 18.00 mmol) and DIPEA (3.85 mL, 22.50 mmol) in DMF (25 mL) was heated at 100° C. for 1 hour. The reaction mixture was evaporated to dryness, redissolved in DCM and washed sequentially with 1M aqueous K2CO3, water and saturated brine. The organic layer was dried over MgSO4, filtered and evaporated. The crude product was triturated with ether and the solid was collected by filtration, washed with ether and dried under vacuum to afford tert-butyl 4-[3-(difluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazine-1-carboxylate (5.05 g, 95%) as a white crystalline solid.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. dissolutionredissolved in DCM
  3. washwashed sequentially with 1M aqueous K2CO3, water and saturated brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was triturated with ether
  8. filtrationthe solid was collected by filtration
  9. washwashed with ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-67098c7b72c3468c8892d0746c4f88dc
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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