Chloroform → 1-(2-{4-[(2,3-dihydrofuro[2,3-c]pyridin-5-ylmethyl)amino]-1-piperidinyl}ethyl)-7-(methyloxy)-2(1H)-quinoxalinone Dihydrochloride

HRID 657090Notes

Reaction equation

HRID 657090 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.[O:23]1[C:27]2=[CH:28][N:29]=[C:30]([CH:32]=O)[CH:31]=[C:26]2[CH2:25][CH2:24]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:59]>CO>[ClH:59].[ClH:59].[O:23]1[C:27]2=[CH:28][N:29]=[C:30]([CH2:32][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=5)[N:13]=[CH:12][C:11]4=[O:22])[CH2:6][CH2:7]3)[CH:31]=[C:26]2[CH2:25][CH2:24]1

Participants

8

Reactant 6

HCID 6212ChloroformHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 12268230Acetoxyborohydride2×HCID 574231162,3-Dihydrofuro[2,3-c]pyridine-5-carbaldehydeHCID 593978381-[2-(4-Aminopiperidin-1-yl)ethyl]-7-methoxyquinoxalin-2(1H)-one

Product 1

HCID 688202121-(2-{4-[(2,3-dihydrofuro[2,3-c]pyridin-5-ylmethyl)amino]-1-piperidinyl}ethyl)-7-(methyloxy)-2(1H)-quinoxalinone DihydrochlorideYield 76%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-[2-(4-amino-1-piperidinyl)ethyl]-7-(methyloxy)-2(1H)-quinoxalinone (see Example 47(a) for a preparation) (50 mg; 0.17 mmol) and 2,3-dihydrofuro[2,3-c]pyridine-5-carbaldehyde (see Example 38(f) for a preparation) (27 mg, 0.18 mmol) in methanol (2 mL) and chloroform (2 mL) was heated under reflux with 3A molecular sieves overnight. The mixture was cooled and sodium triacetoxyborohydride (0.18 g; 0.85 mmol) was added, and the mixture was stirred at room temperature overnight. More aldehyde (30 mg) and acetoxyborohydride (0.180 g) were added, and the mixture was stirred at room temperature overnight. Further additions of aldehyde (5.4 mg) and acetoxyborohydride (36 mg and 6 mg) were made. The mixture was stirred overnight again, then aqueous sodium bicarbonate solution was added to neutralise and the phases were separated. The aqueous phase was extracted four times with 10% methanol-dichloromethane, and the organic fractions were dried and evaporated. Chromatography on silica gel, eluting with 0-20% methanol-dichloromethane gave the free base of the title compound (56 mg, 76%).

Workup

  1. temperatureThe mixture was cooled
  2. stirringthe mixture was stirred at room temperature overnight
  3. stirringThe mixture was stirred overnight again
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted four times with 10% methanol-dichloromethane
  6. customthe organic fractions were dried
  7. customevaporated
  8. washChromatography on silica gel, eluting with 0-20% methanol-dichloromethane

Sources & evidence

ORD record
ord-0b5032c94df049bcb2086a4f0b5292e6
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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