Acetic Acid → 6-[4-[4-[3-(4-Acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine

HRID 2381082Notes

Reaction equation

HRID 2381082 reaction equation
CCN(C(C)C)C(C)C.[N:10]1([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]3[CH2:31][CH2:30][N:29]([C:32]4[CH2:33][CH2:34][C:35]5[N:36]([C:38]([C:41]([F:44])([F:43])[F:42])=[N:39][N:40]=5)[N:37]=4)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.[C:45](O)(=[O:47])[CH3:46].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:45]([N:13]1[CH2:12][CH2:11][N:10]([CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]([CH:26]3[CH2:27][CH2:28][N:29]([C:32]4[CH2:33][CH2:34][C:35]5[N:36]([C:38]([C:41]([F:44])([F:43])[F:42])=[N:39][N:40]=5)[N:37]=4)[CH2:30][CH2:31]3)=[CH:24][CH:25]=2)[CH2:15][CH2:14]1)(=[O:47])[CH3:46]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 685023596-[4-[4-[3-(Piperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazine

Product 1

HCID 468935846-[4-[4-[3-(4-Acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazineYield 46.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.159 mL, 0.92 mmol) was added to 6-[4-[4-[3-(piperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazine (150 mg, 0.31 mmol), acetic acid (0.021 mL, 0.37 mmol) and HATU (139 mg, 0.37 mmol) in DMF (2 mL). The resulting solution was stirred at ambient temperature for 16 hours then 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 give 6-[4-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazine (75 mg, 46.1%) as a solid.

Workup

  1. customthen 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-c94fba69af384e21b1ea604693bc557f
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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