1-Bromo-2-methylbutane → 4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)-N-(2-methylbutyl)benzenesulfonamide

HRID 594172

反応式

HRID 594172 の反応式
[CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH:25]([CH3:27])[CH3:26])=[CH:21][N:20]=3)(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[C:5]([CH3:28])[O:4][N:3]=1.C(N=C(N(C)C)N(C)C)(C)(C)C.Br[CH2:42][CH:43]([CH3:46])[CH2:44][CH3:45]>C(#N)C>[CH3:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]([S:15]([N:18]([C:19]3[CH:24]=[CH:23][C:22]([CH:25]([CH3:26])[CH3:27])=[CH:21][N:20]=3)[CH2:42][CH:43]([CH3:46])[CH2:44][CH3:45])(=[O:17])=[O:16])=[CH:13][CH:14]=2)=[C:5]([CH3:28])[O:4][N:3]=1

参加物

5

反応物 3

HCID 252541-Bromo-2-methylbutaneHCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidineHCID 898760154-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)benzenesulfonamide

生成物 1

HCID 721949364-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)-N-(2-methylbutyl)benzenesulfonamide収率 4.6%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
20 °C

実験手順

To a solution of 4-((3,5-dimethylisoxazol-4-yl)methoxy)-N-(5-isopropylpyridin-2-yl)benzenesulfonamide (156 mg, 0.389 mmol) in acetonitrile (4 mL) stirred in air at 20° C., was added 2-(tert-butyl)-1,1,3,3-tetramethylguanidine (133 mg, 0.777 mmol). The reaction mixture was stirred at 20° C. for 1 hour, then 1-bromo-2-methylbutane (117 mg, 0.777 mmol) was added. The reaction then heated by microwaves to 150° C., for 30 minutes. After cooling the solvent was removed in vacuo and diluted with ethyl acetate. The organic phase was washed with water (5 mL), then dried using a hydrophobic frit. The solvent was removed in vacuo to give the crude product as an orange oil. Purification of the crude was attempted using flash silica (Si) chromatography (0-25% ethylacetate-cyclohexane gradient) followed by mass directed autoprep (ammonium carbonate modifier), however impurities still remained. A final purification using a silica (Si) cartridge (eluting with a gradient of 0-25% ethyl acetate-cyclohexane) provided a small amount of clean product (8.5 mg) as a colourless oil. LCMS (2 min, High pH) Rt 1.48 mins, m/z (ES+) 472 (M+H).

後処理

  1. customThe reaction
  2. temperaturethen heated by microwaves to 150° C., for 30 minutes
  3. temperatureAfter cooling the solvent
  4. customwas removed in vacuo
  5. additiondiluted with ethyl acetate
  6. washThe organic phase was washed with water (5 mL)
  7. customdried
  8. customThe solvent was removed in vacuo
  9. customto give the crude product as an orange oil
  10. customPurification of the crude
  11. customA final purification
  12. washeluting with a gradient of 0-25% ethyl acetate-cyclohexane)

出典と根拠

ORDレコード
ord-5f62b9dab19b43c6b62e1a6e2d9ad25b
出典データセット
uspto-grants-2016_01
特許番号
US09242972B2

関連ノート

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