Methanol → 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

HRID 1019945Notes

Reaction equation

HRID 1019945 reaction equation
B(Br)(Br)Br.C[O:6][C:7]1[CH:16]=[C:15]2[C:10]([N:11]=[CH:12][C:13]([O:17][CH2:18][CH2:19][N:20]3[CH2:25][CH2:24][CH:23]([NH:26][C:27]([C:29]4[CH:30]=[CH:31][C:32]5[S:37][CH2:36][C:35](=[O:38])[NH:34][C:33]=5[CH:39]=4)=[O:28])[CH2:22][CH2:21]3)=[N:14]2)=[CH:9][CH:8]=1.CO>ClCCl>[OH:6][C:7]1[CH:16]=[C:15]2[C:10]([N:11]=[CH:12][C:13]([O:17][CH2:18][CH2:19][N:20]3[CH2:25][CH2:24][CH:23]([NH:26][C:27]([C:29]4[CH:30]=[CH:31][C:32]5[S:37][CH2:36][C:35](=[O:38])[NH:34][C:33]=5[CH:39]=4)=[O:28])[CH2:22][CH2:21]3)=[N:14]2)=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 25134Boron tribromideHCID 468520703-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid {1-[2-(7-methoxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-amide

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 1M boron tribromide in dichloromethane (2.93 mL, 2.93 mmol, 8.0 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-methoxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-amide (190 mg, 0.37 mmol, 1.0 eq) in dichloromethane (2.5 mL). The reaction mixture is stirred at 0° C. for 30 minutes and then at 40° C. for 24 hours. The reaction mixture is cooled down to 0° C. before the addition of methanol (1 mL). Solvents are evaporated and the crude is taken in water (10 mL), the pH is adjusted to 10 by the addition of 1N sodium hydroxide aqueous solution and the resulting aqueous layer is extracted with diclhoromethane (3×10 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-hydroxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-amide as a white lyophilizated powder (28 mg, 30% yield).

Workup

  1. waitat 40° C. for 24 hours
  2. customSolvents are evaporated
  3. additionthe pH is adjusted to 10 by the addition of 1N sodium hydroxide aqueous solution
  4. extractionthe resulting aqueous layer is extracted with diclhoromethane (3×10 mL)
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a residue that
  9. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-384dcdc7060149b28eb27bce0f32af24
Source dataset
uspto-grants-2014_05
Patent number
US08716280B2

Reaction notes

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