Methanol → 2-{[4-({[6-(trifluoromethyl)-3-pyridazinyl]methyl}amino)-1-piperidinyl]methyl}-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione

HRID 420703Notes

Reaction equation

HRID 420703 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH:9]2[N:19]3[C:20]4[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=4[N:16]=[CH:17][C:18]3=[O:21])[CH2:10]2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:30][C:31]1[N:32]=[N:33][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:35][CH:36]=1.CO>CC#N>[F:40][C:37]([F:38])([F:39])[C:34]1[N:33]=[N:32][C:31]([CH2:30][NH:1][CH:2]2[CH2:7][CH2:6][N:5]([CH2:8][CH:9]3[N:19]4[C:20]5[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=5[N:16]=[CH:17][C:18]4=[O:21])[CH2:10]3)[CH2:4][CH2:3]2)=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 580017682-((4-aminopiperidin-1-yl)methyl)-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dioneHCID 585794043-(Bromomethyl)-6-(trifluoromethyl)pyridazine2×

Product 1

HCID 445157132-{[4-({[6-(trifluoromethyl)-3-pyridazinyl]methyl}amino)-1-piperidinyl]methyl}-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dioneYield 30%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 2-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione (for a synthesis see Example 2(j)) (56.3 mg, 0.187 mmol), K2CO3 (34.4 mg, 0.249 mmol) and 3-(bromomethyl)-6-(trifluoromethyl)pyridazine (for a synthesis see Preparation 1 below) (30 mg, 0.124 mmol) in CH3CN (1 ml) and MeOH (0.1 ml) was stirred at room temperature overnight. LCMS showed amine derivative remaining. An excess of 3-(bromomethyl)-6-(trifluoromethyl)pyridazine (25 mg) was added. The mixture was stirred at room temperature for 1 h. The solid was filtered off and the solvent evaporated. Purification by flash chromatography using Flashmaster II and mixtures of DCM and MeOH as eluent afforded 2-{[4-({[6-(trifluoromethyl)-3-pyridazinyl]methyl}amino)-1-piperidinyl]methyl}-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione (17 mg, 30%).

Workup

  1. filtrationThe solid was filtered off
  2. customthe solvent evaporated
  3. customPurification by flash chromatography

Sources & evidence

ORD record
ord-1de0734c826b4f2b854a24ce2194d75a
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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