Diisopropylethylamine → 4-(1-(3-(Trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl)phenol

HRID 2381098Notes

Reaction equation

CCN(C(C)C)C(C)C.Cl[C:11]1[CH:12]=[CH:13][C:14]2[N:15]([C:17]([C:20]([F:23])([F:22])[F:21])=[N:18][N:19]=2)[N:16]=1.[NH:24]1[CH2:29][CH2:28][CH:27]([C:30]2[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=2)[CH2:26][CH2:25]1>CN(C=O)C>[F:21][C:20]([F:23])([F:22])[C:17]1[N:15]2[N:16]=[C:11]([N:24]3[CH2:29][CH2:28][CH:27]([C:30]4[CH:31]=[CH:32][C:33]([OH:36])=[CH:34][CH:35]=4)[CH2:26][CH2:25]3)[CH:12]=[CH:13][C:14]2=[N:19][N:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

DIPEA (48.2 mL, 276.86 mmol) was added to 6-chloro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (obtained as described in Monatsh. Chem. 1972, 103, 1591) (24.65 g, 110.74 mmol) and 4-(piperidin-4-yl)phenol (20.61 g, 116.28 mmol) in DMF (200 mL). The resulting solution was stirred at 80° C. for 1 hour. The reaction mixture was cooled to room temperature, then evaporated to dryness and re-dissolved in DCM (1 L) and washed with water (2×1 L). The organic layer was washed with saturated brine (500 mL), then dried over MgSO4, filtered and evaporated to afford crude product. The crude product was triturated with ether to afford 4-{1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenol (36.6 g, 91%) is as a solid.

Workup

temperatureThe reaction mixture was cooled to room temperature
customevaporated to dryness
dissolutionre-dissolved in DCM (1 L)
washwashed with water (2×1 L)
washThe organic layer was washed with saturated brine (500 mL)
dry with materialdried over MgSO4
filtrationfiltered
customevaporated
customto afford crude product
customThe crude product was triturated with ether

Sources & evidence

ORD record: ord-24647f8638f24deeb4e74954913c0d40
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258140B2

Reaction notes

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