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Diisopropylethylamine → 3-(difluoromethyl)-6-[4-[(1R)-1-(4-fluorophenyl)ethyl]piperazin-1-yl][1,2,4]triazolo[4,3-b]pyridazine

HRID 1674985
Notes
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Reaction equation

HRID 1674985 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.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C@H:21]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH3:22])=[CH:17][CH:16]=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:26]3[CH2:25][CH2:24][N:23]([C@@H:21]([C:18]4[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=4)[CH3:22])[CH2:28][CH2:27]3)[CH:3]=[CH:4][C:5]2=[N:10][N:9]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 14723856-Chloro-3-(difluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazineHCID 16748801(R)-1-(1-(4-Fluorophenyl)ethyl)piperazine

Product 1

HCID 441258313-(difluoromethyl)-6-[4-[(1R)-1-(4-fluorophenyl)ethyl]piperazin-1-yl][1,2,4]triazolo[4,3-b]pyridazineYield 84%

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent

Procedure

A stirred solution of 6-chloro-3-(difluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (103 mg, 0.5 mmol), (R)-1-[1-(4-fluorophenyl)ethyl]piperazine (125 mg, 0.6 mmol) (prepared as described in J. Med. Chem. 2007, 50, 3528) and DIPEA (97 mg, 0.75 mmol, 129 μl) in DMF (2 mL) was heated at 100° C. for 2 hours. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 3-(difluoromethyl)-6-[4-[(1R)-1-(4-fluorophenyl)ethyl]piperazin-1-yl][1,2,4]triazolo[4,3-b]pyridazine (158 mg, 84%) as a crisp foam.

Workup

  1. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  2. additionFractions containing the desired compound
  3. customwere evaporated to dryness

Sources & evidence

ORD record
ord-6650573559ec4ef794de89f187aad54d
Source dataset
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08003649B2

Reaction notes

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