Diisopropylethylamine → N-(2-methoxyethyl)-N-methyl-2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)acetamide

HRID 2381114Notes

Reaction equation

HRID 2381114 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][NH:5][CH3:6].[F:7][C:8]([F:36])([F:35])[C:9]1[N:13]2[N:14]=[C:15]([N:18]3[CH2:23][CH2:22][CH:21]([C:24]4[CH:34]=[CH:33][C:27]([O:28][CH2:29][C:30]([OH:32])=O)=[CH:26][CH:25]=4)[CH2:20][CH2:19]3)[CH2:16][CH2:17][C:12]2=[N:11][N:10]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:1][O:2][CH2:3][CH2:4][N:5]([CH3:6])[C:30](=[O:32])[CH2:29][O:28][C:27]1[CH:26]=[CH:25][C:24]([CH:21]2[CH2:22][CH2:23][N:18]([C:15]3[CH2:16][CH2:17][C:12]4[N:13]([C:9]([C:8]([F:7])([F:36])[F:35])=[N:10][N:11]=4)[N:14]=3)[CH2:19][CH2:20]2)=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 300977(2-Methoxyethyl)(methyl)amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 685023702-[4-[1-[3-(Trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetic acid

Product 1

HCID 46893852N-(2-methoxyethyl)-N-methyl-2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)acetamideYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(2-methoxyethyl)methylamine (25 mg, 0.28 mmol) was added to 2-[4-[1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]phenoxy]acetic acid (100 mg, 0.24 mmol), HATU (108 mg, 0.28 mmol) and DIPEA (0.123 mL, 0.71 mmol) in DMF (2 mL). The resulting solution was stirred at ambient temperature for 3 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 afford N-(2-methoxyethyl)-N-methyl-2-(4-{1-[3-(trifluoromethyl)-7,8-dihydro[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl}phenoxy)acetamide (38 mg, 32%) 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-e33d0feaa46d456e91ab99e5685b88f1
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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