2-(Methylamino)ethanol → N-(2-hydroxyethyl)-N-methyl-4-[[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]oxy]benzamide

HRID 1675052Notes

Reaction equation

HRID 1675052 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]([F:38])([F:37])[C:12]1[N:16]2[N:17]=[C:18]([N:21]3[CH2:26][CH2:25][CH:24]([O:27][C:28]4[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=4)[CH2:23][CH2:22]3)[CH:19]=[CH:20][C:15]2=[N:14][N:13]=1.[CH3:39][NH:40][CH2:41][CH2:42][OH:43].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:43][CH2:42][CH2:41][N:40]([CH3:39])[C:32](=[O:33])[C:31]1[CH:30]=[CH:29][C:28]([O:27][CH:24]2[CH2:23][CH2:22][N:21]([C:18]3[CH:19]=[CH:20][C:15]4[N:16]([C:12]([C:11]([F:37])([F:10])[F:38])=[N:13][N:14]=4)[N:17]=3)[CH2:26][CH2:25]2)=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 80162-(Methylamino)ethanolHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673405034-[[1-[3-(Trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]oxy]benzoic acid

Product 1

HCID 59149747N-(2-hydroxyethyl)-N-methyl-4-[[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]oxy]benzamideYield 55.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.087 mL, 0.5 mmol) was added to 4-[[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]oxy]benzoic acid (100 mg, 0.25 mmol), 2-(methylamino)ethanol (20.28 mg, 0.27 mmol) and HATU (114 mg, 0.3 mmol) in DMF (2 mL). The resulting solution was stirred at room temperature for 24 hours. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 21 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 N-(2-hydroxyethyl)-N-methyl-4-[[1-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]oxy]benzamide (64 mg, 55%).

Workup

  1. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 21 mm diameter, 100 mm length)
  2. additionFractions containing the desired compound
  3. customwere evaporated to dryness

Sources & evidence

ORD record
ord-e0c4d81e640347f5907aa4e25033628e
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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