1,4-Dioxane → HCID 57970171, compound

HRID 1666662Notes

Reaction equation

HRID 1666662 reaction equation
Cl[C:2]1[CH:11]=[C:10]([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.[CH2:15]([N:22]1[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O1CCOCC1.CC(C)([O-])C.[Na+]>C(OCC)(=O)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:15]([N:22]1[CH2:26][CH2:25][C@H:24]([NH:27][C:2]2[CH:11]=[C:10]([CH3:12])[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=3)[N:3]=2)[CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 2247882-Chloro-6-methoxy-4-methylquinolineHCID 1519353(3S)-(+)-1-Benzyl-3-aminopyrrolidineHCID 23676156Sodium t-butoxide

Product 1

HCID 57970171HCID 57970171, compoundYield 59.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a mixture of 2-chloro-6-methoxy-4-methylquinoline (1.1 g), Pd2(dba)3 (0.242 g), (±)-BINAP (0.495 g), (S)-1-benzyl-3-aminopyrrolidine (1.1 g), and 1,4-dioxane (88 mL) was added sodium t-butoxide (1.65 g) under nitrogen atmosphere, and the mixture was stirred at 65° C. for 3 h. The reaction mixture was diluted with ethyl acetate and water, then the interlayer was removed by Celite filtration, and the organic layer was washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, then the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, hexane/ethyl acetate=10:1) to obtain (S)-N-(1-benzylpyrrolidin-3-yl)-6-methoxy-4-methylquinolin-2-amine (1.1 g). (2) (S)-N-(1-Benzylpyrrolidin-3-yl)-6-methoxy-4-methylquinolin-2-amine (1.1 g) was dissolved in methanol (25 mL), followed by addition of 20% Pd(OH)2/C (0.20 g), and the mixture was stirred at 45° C. under hydrogen atmosphere for 5 h. The catalyst was removed by Celite filtration, and then the filtrate was concentrated under reduced pressure to obtain (S)-6-methoxy-4-methyl-N-(pyrrolidin-3-yl)quinolin-2-amine (0.81 g).

Workup

  1. customthe interlayer was removed by Celite filtration
  2. washthe organic layer was washed with saturated brine
  3. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  4. customthe desiccant was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (NH silica gel, hexane/ethyl acetate=10:1)

Sources & evidence

ORD record
ord-97aa00ccbda7490f8ad5f5abdb44f10c
Source dataset
uspto-grants-2011_10
Patent number
US08044068B2

Reaction notes

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