Ethyl Bromide → 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid {1-[2-(7-ethoxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-amide

HRID 1019946Notes

Reaction equation

HRID 1019946 reaction equation
[CH2:1](Br)[CH3:2].[OH:4][C:5]1[CH:14]=[C:13]2[C:8]([N:9]=[CH:10][C:11]([O:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][CH:21]([NH:24][C:25]([C:27]4[CH:28]=[CH:29][C:30]5[S:35][CH2:34][C:33](=[O:36])[NH:32][C:31]=5[CH:37]=4)=[O:26])[CH2:20][CH2:19]3)=[N:12]2)=[CH:7][CH:6]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:1]([O:4][C:5]1[CH:14]=[C:13]2[C:8]([N:9]=[CH:10][C:11]([O:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][CH:21]([NH:24][C:25]([C:27]4[CH:28]=[CH:29][C:30]5[S:35][CH2:34][C:33](=[O:36])[NH:32][C:31]=5[CH:37]=4)=[O:26])[CH2:20][CH2:19]3)=[N:12]2)=[CH:7][CH:6]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 11430Potassium CarbonateHCID 1363794043-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid {1-[2-(7-hydroxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-amide

Product 1

HCID 468531763-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid {1-[2-(7-ethoxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-amideYield 18.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl bromide (12.8 μL, 0.17 mmol, 1.1 eq) is added at room temperature to a stirred solution of 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid {1-[2-(7-hydroxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-amide (75 mg, 0.16 mmol, 1.0 eq) in N,N-dimethylformamide (2 mL), followed by potassium carbonate (28.1 mg, 0.20 mmol, 1.3 eq). After 3 hours stirring at 60° C., solvent is evaporated and the residue is extracted with dichloromethane (3×5 mL) and water (5 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by preparative HPLC to afford 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid {1-[2-(7-ethoxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-amide as a white powder (15 mg, 18% yield).

Workup

  1. customsolvent is evaporated
  2. extractionthe residue is extracted with dichloromethane (3×5 mL) and water (5 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-cd994342c3d64840b686f660a3493c90
Source dataset
uspto-grants-2014_05
Patent number
US08716280B2

Reaction notes

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