Sodium Bicarbonate → 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)-3-fluoropiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one

HRID 2193382Notes

Reaction equation

HRID 2193382 reaction equation
[F:1][CH:2]1[C:7](=O)[CH2:6][CH2:5][N:4]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][C:12]2=[O:23])[CH2:3]1.[O:24]1[C:33]2[CH:32]=[C:31]([CH2:34][NH2:35])[N:30]=[CH:29][C:28]=2[O:27][CH2:26][CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(O)(=O)C.ClCCl>[O:24]1[C:33]2[CH:32]=[C:31]([CH2:34][NH:35][CH:7]3[CH2:6][CH2:5][N:4]([CH2:9][CH2:10][N:11]4[C:20]5[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=5)[N:14]=[CH:13][C:12]4=[O:23])[CH2:3][CH:2]3[F:1])[N:30]=[CH:29][C:28]=2[O:27][CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 593981871-(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-yl)methanamineHCID 593983671-(2-(3-fluoro-4-oxopiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one

Product 1

HCID 250084121-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)-3-fluoropiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-oneYield 43.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To 2 mL of a dichloromethane solution containing 48 mg of 1-(2-(3-fluoro-4-oxopiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one and 30 mg of 1-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-yl)methaneamine, 26 μL of acetic acid was added, and stirred at room temperature for 1.5 hours. To the reaction mixture, 48 mg of sodium triacetoxyborohydride was added, and stirred for 1.5 hours. To the reaction mixture, aqueous saturated sodium hydrogen carbonate solution and chloroform were added, the organic layer was separated, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by basic silica gel column chromatography [eluent; chloroform:methanol=50:1], to give 31 mg of 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)-3-fluoropiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one as a brown oil.

Workup

  1. additionwas added
  2. stirringstirred for 1.5 hours
  3. customthe organic layer was separated
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue thus obtained
  7. customwas purified by basic silica gel column chromatography [eluent; chloroform:methanol=50:1]

Sources & evidence

ORD record
ord-64237e45ba894ed189f6826ccaf7e679
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

Loading…