Acetyl chloride → acetic 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 1019947Notes

Reaction equation

HRID 1019947 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[OH:5][C:6]1[CH:15]=[C:14]2[C:9]([N:10]=[CH:11][C:12]([O:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][CH:22]([NH:25][C:26]([C:28]4[CH:29]=[CH:30][C:31]5[S:36][CH2:35][C:34](=[O:37])[NH:33][C:32]=5[CH:38]=4)=[O:27])[CH2:21][CH2:20]3)=[N:13]2)=[CH:8][CH:7]=1.C(N(CC)CC)C>CN(C)C=O>[O:37]=[C:34]1[NH:33][C:32]2[CH:38]=[C:28]([C:26]([NH:25][CH:22]3[CH2:23][CH2:24][N:19]([CH2:18][CH2:17][O:16][C:12]4[CH:11]=[N:10][C:9]5[C:14]([N:13]=4)=[CH:15][C:6]([O:5][C:1](=[O:3])[CH3:2])=[CH:7][CH:8]=5)[CH2:20][CH2:21]3)=[O:27])[CH:29]=[CH:30][C:31]=2[S:36][CH2:35]1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 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 66746242acetic 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 44.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Acetyl chloride (11.4 μL, 0.16 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 (70 mg, 0.15 mmol, 1.0 eq) in N,N-dimethylformamide (2 mL), followed by triethylamine (40.7 μL, 0.29 mmol, 2.0 eq). After 1 hour 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 acetic 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 a white powder (35 mg, 41% 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-88df454ce28149f9b297e93de0bfdbce
Source dataset
uspto-grants-2014_05
Patent number
US08716280B2

Reaction notes

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