Sodium Bicarbonate → (2S)-2-{[4-(6-methoxyquinolin-2-yl)piperazin-1-yl]methyl]-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

HRID 860016Notes

Reaction equation

HRID 860016 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)[CH:7]=[CH:6]2.[CH3:19][C:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25]3[O:33][CH2:32][C@H:31]([CH2:34]OS(C4C=CC(Br)=CC=4)(=O)=O)[O:30][C:26]3=2)[N:21]=1.C(=O)(O)[O-].[Na+]>CS(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([N:13]1[CH2:18][CH2:17][N:16]([CH2:34][C@@H:31]3[O:30][C:26]4=[C:27]5[C:22](=[CH:23][CH:24]=[C:25]4[O:33][CH2:32]3)[N:21]=[C:20]([CH3:19])[CH:29]=[CH:28]5)[CH2:15][CH2:14]1)[CH:7]=[CH:6]2

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 20624762[(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl4-bromobenzenesulfonateHCID 216804206-Methoxy-2-piperazin-1-yl-quinoline

Product 1

HCID 58765328(2S)-2-{[4-(6-methoxyquinolin-2-yl)piperazin-1-yl]methyl]-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolineYield 48.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-methoxy-2-piperazin-1-yl-quinoline of Step D (1.05 g, 4.31 mmol) in dimethylsulfoxide (15 mL) and [(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl-4-bromobenzene sulfonate (1.62 g) is heated at 80° C. under nitrogen for 3 hours and at 90° C. for 1 additional hour. The solution is poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The extracts are dried over anhydrous magnesium sulfate and evaporated to dryness. The residue is flash chromatographed on silica gel Merck-60 using a gradient of methanol (0.5–3%) in dichloromethane-hexane (1:1) containing 0.1% ammonium hydroxide to provide the title compound (0.790 g). The pure material is charcoalized (in ethyl acetate), filtered, evaporated and induced to crystallize from hexane by sonication. The off-white solid melts at 158–160° C.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe extracts are dried over anhydrous magnesium sulfate
  3. customevaporated to dryness
  4. customchromatographed on silica gel Merck-60
  5. additioncontaining 0.1% ammonium hydroxide

Sources & evidence

ORD record
ord-012f9d6c899e4dd9b08a8dc4d4c6ea53
Source dataset
uspto-grants-2006_12
Patent number
US07153849B2

Reaction notes

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