Triethylamine → 6-[4-[4-[2-[4-(Methylsulfonyl)piperazin-1-yl]ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

HRID 1675158Notes

Reaction equation

HRID 1675158 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[N:6]1([CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:26][CH2:25][N:24]([C:27]4[CH:28]=[CH:29][C:30]5[N:31]([C:33]([C:36]([F:39])([F:38])[F:37])=[N:34][N:35]=5)[N:32]=4)[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.C(N(CC)CC)C>C(Cl)Cl.O>[CH3:1][S:2]([N:9]1[CH2:10][CH2:11][N:6]([CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:26][CH2:25][N:24]([C:27]4[CH:28]=[CH:29][C:30]5[N:31]([C:33]([C:36]([F:39])([F:37])[F:38])=[N:34][N:35]=5)[N:32]=4)[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:7][CH2:8]1)(=[O:4])=[O:3]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 667881436-[4-[4-(2-Piperazin-1-ylethoxy)phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

Product 1

HCID 591497976-[4-[4-[2-[4-(Methylsulfonyl)piperazin-1-yl]ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazineYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of methanesulfonyl chloride (0.034 mL, 0.44 mmol) in DCM (0.5 mL) was added dropwise to 6-[4-[4-(2-piperazin-1-ylethoxy)phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (obtained as described in Example 727) (175 mg, 0.37 mmol) and triethylamine (0.103 mL, 0.74 mmol) in DCM (1 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 5 minutes then allowed to warm to room temperature and stirred for a further 15 minutes. The reaction mixture was diluted with water (2 mL), passed through a phase separating cartridge then the organic layer evaporated to afford crude product. 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 6-[4-[4-[2-[4-(methylsulfonyl)piperazin-1-yl]ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (122 mg, 60%).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for a further 15 minutes
  3. customseparating cartridge
  4. customthe organic layer evaporated
  5. customto afford crude product
  6. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  7. additionFractions containing the desired compound
  8. customwere evaporated to dryness

Sources & evidence

ORD record
ord-61f36f0d1f624046971bd8a35172d7a9
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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