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

HRID 1364500노트

반응식

HRID 1364500 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:40])[O:39][C:37](=[O:38])[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:40])[CH2:35][CH2:36][C:37]([OH:39])=[O:38])(=[O:25])=[O:26])=[CH:20][CH:19]=2)[N:3]=1

참가 물질

6

반응물 3

HCID 7922Succinic anhydrideHCID 5330790Jnj-7706621HCID 23665647Potassium tert-butoxide

생성물 1

HCID 115984324-{4-[5-amino-1-(2,6-difluoro-benzoyl)-1H-[1,2,4]triazol-3-ylamino]-benzenesulfonylamino}-4-oxo-butyric acid수율 31%

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 (0.10 g, 0.25 mmol) and THF (10 mL). The mixture was cooled to 0° C. and potassium tert-butoxide (0.28 mL, 1.0 M solution in THF) was added dropwise. After addition the mixture was stirred at 0° C. for 1 hr, then succinic anhydride (28 mg in 5 mL THF, 0.28 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 (39 mg, 31%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 7.70 (d, 2H), 7.63 (m, 1H), 7.42 (d, 2H), 7.15 (t, 2H), 2.41 (br s, 4H); 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-970c51e705234409bcd2700beb27eb9c
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07888380B2

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