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 1019945노트

반응식

HRID 1019945 반응식
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

참가 물질

5

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-384dcdc7060149b28eb27bce0f32af24
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716280B2

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