Triethylamine → methanesulfonic acid 3-(2-{4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-piperidin-1-yl}-ethoxy)-quinoxalin-6-yl ester

HRID 2279382Notes

Reaction equation

HRID 2279382 reaction equation
CS([O:5][S:6]([CH3:9])(=[O:8])=[O:7])(=O)=O.O[C:11]1[CH:20]=[C:19]2[C:14]([N:15]=[CH:16][C:17]([O:21][CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][CH:27]([NH:30][C:31]([C:33]4[CH:34]=[CH:35][C:36]5[S:41][CH2:40][C:39](=[O:42])[NH:38][C:37]=5[CH:43]=4)=[O:32])[CH2:26][CH2:25]3)=[N:18]2)=[CH:13][CH:12]=1.C(N(CC)CC)C>CN(C)C=O>[O:42]=[C:39]1[NH:38][C:37]2[CH:43]=[C:33]([C:31]([NH:30][CH:27]3[CH2:26][CH2:25][N:24]([CH2:23][CH2:22][O:21][C:17]4[CH:16]=[N:15][C:14]5[C:19]([N:18]=4)=[CH:20][C:11]([O:5][S:6]([CH3:9])(=[O:7])=[O:8])=[CH:12][CH:13]=5)[CH2:29][CH2:28]3)=[O:32])[CH:34]=[CH:35][C:36]=2[S:41][CH2:40]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 81560Methanesulfonic anhydrideHCID 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 86662006methanesulfonic acid 3-(2-{4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-piperidin-1-yl}-ethoxy)-quinoxalin-6-yl esterYield 29.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methanesulfonic anhydride (519 mg, 2.92 mmol, 20.0 eq) is added at 0° C. 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 (70 mg, 0.15 mmol, 1.0 eq) in N,N-dimethylformamide (2 mL), followed by triethylamine (610.4 μL, 4.38 mmol, 30.0 eq). After 30 minutes 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 methanesulfonic acid 3-(2-{4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-piperidin-1-yl}-ethoxy)-quinoxalin-6-yl ester as an off-white powder (25 mg, 26% 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-f40228540de34883ab9eb51dfc93cb0e
Source dataset
uspto-grants-2015_09
Patent number
US09133219B2

Reaction notes

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