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ノート

反応式

HRID 2068993 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-5698ded532bc46b6a26b91168798e33f
出典データセット
uspto-grants-2012_10
特許番号
US08299082B2

反応ノート

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