Chloroform → 1-(2-{4-[(6,7-dihydro[1,4]dioxino[2,3-c]pyridazin-3-ylmethyl)amino]-1-piperidinyl}ethyl)-7-(methyloxy)-2(1H)-quinoxalinone dihydrochloride

HRID 656994Notes

Reaction equation

HRID 656994 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[N:23]1[C:28]2[O:29][CH2:30][CH2:31][O:32][C:27]=2[CH:26]=[C:25]([CH:33]=O)[N:24]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O[BH3-])(=O)C.C(=O)(O)[O-].[Na+].C(Cl)(Cl)[Cl:60]>CO>[ClH:60].[ClH:60].[N:23]1[C:28]2[O:29][CH2:30][CH2:31][O:32][C:27]=2[CH:26]=[C:25]([CH2:33][NH:1][CH:2]2[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=4)[N:13]=[CH:12][C:11]3=[O:22])[CH2:6][CH2:7]2)[N:24]=1

Participants

8

Reactant 6

HCID 6212ChloroformHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 12268230AcetoxyborohydrideHCID 248916966,7-Dihydro-[1,4]dioxino[2,3-c]pyridazine-3-carbaldehydeHCID 593978381-[2-(4-Aminopiperidin-1-yl)ethyl]-7-methoxyquinoxalin-2(1H)-one

Product 1

HCID 689925981-(2-{4-[(6,7-dihydro[1,4]dioxino[2,3-c]pyridazin-3-ylmethyl)amino]-1-piperidinyl}ethyl)-7-(methyloxy)-2(1H)-quinoxalinone dihydrochlorideYield 52%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-[2-(4-amino-1-piperidinyl)ethyl]-7-(methyloxy)-2(1H)-quinoxalinone (200 mg; 0.66 mmol) and 6,7-dihydro[1,4]dioxino[2,3-c]pyridazine-3-carbaldehyde (116 mg, 0.70 mmol) in MeOH (8 mL) and chloroform (8 mL) was heated under reflux with 3A molecular sieves overnight. It was cooled and sodium triacetoxyborohydride (0.54 g; 2.55 mmol) was added, and the mixture was stirred at rt overnight. More aldehyde (20 mg) and acetoxyborohydride (100 mg) were added, and this was repeated after 7 h. The mixture was left stirring for three days, then aqueous sodium bicarbonate solution was added to basify and the phases were separated. The aqueous phase was extracted three times with 10% MeOH-DCM, and the organic fractions were dried and evaporated. Chromatography on silica gel, eluting with 0-20% MeOH-DCM gave the free base of the title compound (155 mg, 52%).

Workup

  1. temperatureIt was cooled
  2. waitthis was repeated after 7 h
  3. waitThe mixture was left
  4. stirringstirring for three days
  5. customthe phases were separated
  6. extractionThe aqueous phase was extracted three times with 10% MeOH-DCM
  7. customthe organic fractions were dried
  8. customevaporated
  9. washChromatography on silica gel, eluting with 0-20% MeOH-DCM

Sources & evidence

ORD record
ord-ea26dbfe59ac4e9b80b0f5e2527718a2
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

Loading…