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

HRID 860012Notes

Reaction equation

HRID 860012 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]3[O:15][CH2:14][CH:13]([CH2:16][N:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[O:12][C:8]3=2)[N:3]=1.[Br:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[N:30]=[C:29](Cl)[CH:28]=[CH:27]2.C(=O)(O)[O-].[Na+]>>[Br:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[N:30]=[C:29]([N:20]1[CH2:21][CH2:22][N:17]([CH2:16][C@@H:13]3[O:12][C:8]4=[C:9]5[C:4](=[CH:5][CH:6]=[C:7]4[O:15][CH2:14]3)[N:3]=[C:2]([CH3:1])[CH:11]=[CH:10]5)[CH2:18][CH2:19]1)[CH:28]=[CH:27]2

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 128940866-Bromo-2-chloroquinolineHCID 696050258-Methyl-2-piperazin-1-ylmethyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

Product 1

HCID 44219922(2S)-2-{[4-(6-Bromoquinolin-2-yl)piperazin-1-yl]methyl}-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

Conditions

Temperature
95 °C

Procedure

A mixture of 8-methyl-2-piperazin-1-ylmethyl-2,3-dihydro-[1,4]dioxino[2,3-f]quinoline of Step B′ (0.493 g, 1.64 mmol) and 6-bromo-2-chloroquinoline of Example 1, Step A (0.507 g) is heated at 95° C. under nitrogen for 6 hours, followed by heating at 105° C. for 4 hours. The mixture is cooled, 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 Merck-60 using a gradient of methanol (0.5–2%) in dichloromethane-hexane (45:55), to provide the title compound (0.147 g) identical to the compound of Example 27, Step C.

Workup

  1. temperatureby heating at 105° C. for 4 hours
  2. temperatureThe mixture is cooled
  3. extractionextracted with ethyl acetate
  4. dry with materialThe extracts are dried over anhydrous magnesium sulfate
  5. customevaporated to dryness
  6. customchromatographed on silica Merck-60

Sources & evidence

ORD record
ord-a3db8912a6ef4c60a58325615e888f76
Source dataset
uspto-grants-2006_12
Patent number
US07153849B2

Reaction notes

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