Diisopropylethylamine → 4-Pyridin-3-yl-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol
Reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([F:14])([F:13])[F:12])=[N:9][N:10]=2)[N:7]=1.[N:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]2([OH:27])[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[CH:16]=1.C(N(C(C)C)C(C)C)C>CN(C=O)C.O>[N:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]2([OH:27])[CH2:22][CH2:23][N:24]([C:2]3[CH:3]=[CH:4][C:5]4[N:6]([C:8]([C:11]([F:14])([F:13])[F:12])=[N:9][N:10]=4)[N:7]=3)[CH2:25][CH2:26]2)[CH:16]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
A stirred solution of 6-chloro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (16.69 g, 75 mmol), 4-(pyridin-3-yl)piperidin-4-ol (14.70 g, 82.50 mmol) and N-ethyldiisopropylamine (16.98 mL, 97.50 mmol) in DMF (75 mL) was heated at 80° C. for 1 hr. The solution was cooled to ambient temperature and slowly diluted with water, with seeding, giving a crystalline precipitate. The precipitate was collected by filtration, washed with water, acetonitrile and ether and dried under vacuum at 50° C. to afford 4-(pyridin-3-yl)-1-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-ol anhydrous Form A (25.2 g, 92%) as a cream crystalline solid, which was used without further purification. Approximately 30 mg of material was then slurried in approximately 1 ml of ethyl acetate and stirred using a magnetic stirrer bar for 3 days at ambient temperature. The resultant material was air dried and analysed.
Workup
- customgiving a crystalline precipitate
- filtrationThe precipitate was collected by filtration
- washwashed with water, acetonitrile and ether
- customdried under vacuum at 50° C.
Sources & evidence
- ORD record
- ord-c6ea4e7fac6e464ea6da5c5ef49efe8d
- Source dataset
- uspto-grants-2011_08
- Patent number
- US08003649B2
Reaction notes
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