Potassium Carbonate → [3-(2-{4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-piperidin-1-yl}-ethoxy)-quinoxalin-6-yloxy]-acetic acid methyl ester

HRID 1019949Notes

Reaction equation

HRID 1019949 reaction equation
[CH3:1][O:2][C:3](=[O:6])[CH2:4]Br.[OH:7][C:8]1[CH:17]=[C:16]2[C:11]([N:12]=[CH:13][C:14]([O:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][CH:24]([NH:27][C:28]([C:30]4[CH:31]=[CH:32][C:33]5[S:38][CH2:37][C:36](=[O:39])[NH:35][C:34]=5[CH:40]=4)=[O:29])[CH2:23][CH2:22]3)=[N:15]2)=[CH:10][CH:9]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:1][O:2][C:3](=[O:6])[CH2:4][O:7][C:8]1[CH:17]=[C:16]2[C:11](=[CH:10][CH:9]=1)[N:12]=[CH:13][C:14]([O:18][CH2:19][CH2:20][N:21]1[CH2:22][CH2:23][CH:24]([NH:27][C:28]([C:30]3[CH:31]=[CH:32][C:33]4[S:38][CH2:37][C:36](=[O:39])[NH:35][C:34]=4[CH:40]=3)=[O:29])[CH2:25][CH2:26]1)=[N:15]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 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 66747595[3-(2-{4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-piperidin-1-yl}-ethoxy)-quinoxalin-6-yloxy]-acetic acid methyl esterYield 6.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Bromo-acetic acid methyl ester (20.0 μL, 0.22 mmol, 1.05 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 (100 mg, 0.21 mmol, 1.0 eq) in N,N-dimethylformamide (2 mL), followed by potassium carbonate (57.6 mg, 0.42 mmol, 2.0 eq). After 5 hours stirring at room temperature, 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-(2-{4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-piperidin-1-yl}-ethoxy)-quinoxalin-6-yloxy]-acetic acid methyl ester as a white powder (8 mg, 6% 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-65a0d3634f0e47b78d32894ec07497e9
Source dataset
uspto-grants-2014_05
Patent number
US08716280B2

Reaction notes

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