Glutaric anhydride → 5-{4-[5-amino-1-(2,6-difluoro-benzoyl)-1H-[1,2,4]triazol-3-ylamino]-benzenesulfonylamino}-5-oxo-pentanoic acid

HRID 2068993

반응식

HRID 2068993 반응식
[NH2:1][C:2]1[N:6]([C:7](=[O:16])[C:8]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=2[F:15])[N:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)[N:3]=1.CC(C)([O-])C.[K+].[C:34]1(=[O:41])[O:40][C:38](=[O:39])[CH2:37][CH2:36][CH2:35]1>C(O)(=O)C.C1COCC1>[NH2:1][C:2]1[N:6]([C:7](=[O:16])[C:8]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=2[F:15])[N:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([NH:27][C:34](=[O:41])[CH2:35][CH2:36][CH2:37][C:38]([OH:40])=[O:39])(=[O:25])=[O:26])=[CH:20][CH:19]=2)[N:3]=1

참가 물질

6

반응물 3

HCID 7940Glutaric anhydrideHCID 5330790Jnj-7706621HCID 23665647Potassium tert-butoxide

생성물 1

HCID 116563845-{4-[5-amino-1-(2,6-difluoro-benzoyl)-1H-[1,2,4]triazol-3-ylamino]-benzenesulfonylamino}-5-oxo-pentanoic acid

시약·촉매·용매 2

HCID 176Acetic Acid촉매HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

To a nitrogen purged flask was added 4-[5-amino-1-(2,6-difluorobenzoyl)-1H-[1,2,4]triazol-3-ylamino]-benzenesulfonamide Compound 1a (2.0 g, 5.1 mmol) and THF (200 mL). The mixture was cooled to 0° C. and potassium tert-butoxide (6.1 mL, 1.0 M solu in THF) was added dropwise. After addition the mixture was stirred at 0° C. for 1 hr, then glutaric anhydride (0.69 g in 10 mL THF, 6.0 mmol) was added dropwise. The stirring was continued for 30 min, then the mixture was warmed to rt and stirred overnight. A few drops of acetic acid was added, then the mixture was concentrated. The residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH/8:2) to afford the desired product Compound 11 (670 mg, 26%) as a white solid. NMR (300 MHz, CD3OD) δ 7.75 (d, J=7.0 Hz, 2H), 7.68 (m, 1H), 7.50 (d, J=6.9 Hz, 2H), 7.15 (t, J=6.9 Hz, 2H), 2.36 (t, J=6.8 Hz, 2H), 1.80 (t, J=6.8 Hz, 2H); MS (ESI) m/z: 493 (M+H)+.

후처리

  1. additionAfter addition the mixture
  2. waitThe stirring was continued for 30 min
  3. temperaturethe mixture was warmed to rt
  4. stirringstirred overnight
  5. concentrationthe mixture was concentrated
  6. customThe residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH/8:2)

출처 및 근거

ORD 기록
ord-5698ded532bc46b6a26b91168798e33f
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299082B2

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