Sulfuric Acid → N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[3-methylisoxazol-5-yl]phenyl)pyridine-3-sulphonamide

HRID 361450ノート

反応式

HRID 361450 の反応式
C([Li])CCC.[CH3:6][C:7](=[N:9][OH:10])[CH3:8].CO[C:13]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:26]([S:27]([NH:30][C:31]3[C:36]([O:37][CH3:38])=[N:35][C:34]([CH3:39])=[CH:33][N:32]=3)(=[O:29])=[O:28])=[CH:25][CH:24]=[CH:23][N:22]=2)=[CH:17][CH:16]=1)=O.S(=O)(=O)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>CCCCC.C1COCC1.O>[CH3:38][O:37][C:36]1[C:31]([NH:30][S:27]([C:26]2[C:21]([C:18]3[CH:17]=[CH:16][C:15]([C:13]4[O:10][N:9]=[C:7]([CH3:8])[CH:6]=4)=[CH:20][CH:19]=3)=[N:22][CH:23]=[CH:24][CH:25]=2)(=[O:29])=[O:28])=[N:32][CH:33]=[C:34]([CH3:39])[N:35]=1

参加物

9

反応物 5

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 67180Acetone, oximeHCID 211863122-(4-methoxycarbonylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamideHCID 178418339Butyllithium

生成物 1

HCID 21186357N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[3-methylisoxazol-5-yl]phenyl)pyridine-3-sulphonamide収率 8.5%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8003Pentane溶媒HCID 8028Tetrahydrofuran溶媒3 回

実験手順

n-Butyl lithium (1.63 ml of a 1.6M solution in pentane) was added to a stirred solution of acetone oxime (95 mg) in dry THF (5 ml) at 0° C. After 1 hour a solution of 2-(4-methoxycarbonylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (414 mg) in THF (5 ml) was added. The solution was allowed to warm up over 17 hours. The mixture was poured into a stirred solution of concentrated sulphuric acid (0.6 g) in THF (2.8 ml) and water (0.7 ml) and heated under reflux for 1 hour. The cooled solution was treated with saturated sodium carbonate solution to pH 5 then extracted three times with ethyl acetate. The organic extracts were washed with water and saturated sodium chloride solution then dried (MgSO4). Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column, eluting with 0-45% ethyl acetate/hexane to give N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[3-methylisoxazol-5-yl]phenyl)pyridine-3-sulphonamide (37 mg) as a solid; 1H NMR (DMSO-d6 at 373 K); 2.2 (s, 3 H), 2.3 (s, 3 H), 3.8 (s, 3 H), 6.7 (s, 1 H), 7.4 (br s, 1 H), 7.5-7.7 (m, 4 H), 7.8 (d, 2 H), 8.5 (dd, 1 H), 8.8 (dd, 1 H); mass spectrum (+ve ESP): 438 (M+H)+.

後処理

  1. temperatureto warm up over 17 hours
  2. temperatureheated
  3. temperatureunder reflux for 1 hour
  4. extractionthen extracted three times with ethyl acetate
  5. washThe organic extracts were washed with water and saturated sodium chloride solution
  6. dry with materialthen dried (MgSO4)
  7. customVolatile material was removed by evaporation
  8. customthe residue was purified by chromatography on a silica gel Mega Bond Elut column
  9. washeluting with 0-45% ethyl acetate/hexane

出典と根拠

ORDレコード
ord-05dab75ec8124e4e96278259a1a76bb2
出典データセット
uspto-grants-1999_02
特許番号
US05866568

反応ノート

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