2,3-Dihydro-1,4-benzodioxin-6-methylamine → 1-(2-(4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)cyclohexyl)ethyl)-7-methoxy-4-methylquinolin-2(1H)-one

HRID 39853

Reaction equation

HRID 39853 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([CH3:25])=[CH:8][C:9](=[O:24])[N:10]2[CH2:13][CH2:14][C:15]2(C#N)[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]2)=[CH:5][CH:4]=1.[O:26]1[CH2:31][CH2:30][O:29][C:28]2[CH:32]=[C:33]([CH2:36][NH2:37])[CH:34]=[CH:35][C:27]1=2.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(O)(=O)C.C(O)C.ClCCl>[O:26]1[C:27]2[CH:35]=[CH:34][C:33]([CH2:36][NH:37][CH:18]3[CH2:17][CH2:16][CH:15]([CH2:14][CH2:13][N:10]4[C:11]5[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=5)[C:7]([CH3:25])=[CH:8][C:9]4=[O:24])[CH2:20][CH2:19]3)=[CH:32][C:28]=2[O:29][CH2:30][CH2:31]1

Participants

9

Reactant 4

HCID 871022,3-Dihydro-1,4-benzodioxin-6-methylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 675396281-(2-(7-methoxy-4-methyl-2-oxoquinolin-1(2H)-yl)ethyl)-4-oxocyclohexanecarbonitrile

Product 1

HCID 593984071-(2-(4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)cyclohexyl)ethyl)-7-methoxy-4-methylquinolin-2(1H)-oneYield 44.7%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of 3 mL of ethanol and 3 mL of dichloromethane solution containing 0.18 g of 1-(2-(7-methoxy-4-methyl-2-oxoquinolin-1(2H)-yl)ethyl)-4-oxocyclohexanecarbonitrile, 1 mL of ethanol solution containing 0.13 g of (2,3-dihydrobenzo[b][1,4-]dioxin-6-yl)methylamine, 0.30 g of molecular sieves 3A, and 45 μL of acetic acid were added at room temperature. After stirred at 40° C. for 1.5 hours, the mixture was cooled to the room temperature, 36 mg of sodium cyanoborohydride was added, and stirred at the same temperature for 15 min. To the reaction mixture, aqueous saturated sodium hydrogen carbonate solution and chloroform were added, the organic layer was separated, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by flash silica gel column chromatography [hexane:ethyl acetate=4:1], to give (A) 36 mg of 4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)-1-(2-(7-methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)cyclohexanecarbonitrile as a colorless oil and (B) 0.11 g of 4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)-1-(2-(7-methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)cyclohexanecarbonitrile as a white foam.

Workup

  1. additionwere added at room temperature
  2. additionwas added
  3. stirringstirred at the same temperature for 15 min
  4. customthe organic layer was separated
  5. washwashed with aqueous saturated sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customThe residue thus obtained
  9. customwas purified by flash silica gel column chromatography [hexane:ethyl acetate=4:1]

Sources & evidence

ORD record
ord-ad125c172a2441629fd8ab4adf51811e
Source dataset
uspto-grants-2013_09
Patent number
US08524738B2

Linked notes

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