Sodium Iodide → 3-{[3-Cyano-5-cyclopropyl-2-(4-fluorophenyl)-1-benzofuran-6-yl](methylsulfonyl)amino}propane-1-sulfonamide

HRID 705356ノート

反応式

HRID 705356 の反応式
[C:1]([C:3]1[C:7]2[CH:8]=[C:9]([CH:17]3[CH2:19][CH2:18]3)[C:10]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[CH:11][C:6]=2[O:5][C:4]=1[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)#[N:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:34][CH2:35][CH2:36][S:37]([NH2:40])(=[O:39])=[O:38].[I-].[Na+]>CS(C)=O.C(OCC)(=O)C>[C:1]([C:3]1[C:7]2[CH:8]=[C:9]([CH:17]3[CH2:18][CH2:19]3)[C:10]([N:12]([S:13]([CH3:16])(=[O:15])=[O:14])[CH2:34][CH2:35][CH2:36][S:37]([NH2:40])(=[O:39])=[O:38])=[CH:11][C:6]=2[O:5][C:4]=1[C:20]1[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=1)#[N:2]

参加物

7

反応物 4

HCID 5238Sodium Iodide3 回HCID 11430Potassium Carbonate3 回HCID 136148183-Chloropropane-1-sulfonamide3 回HCID 89955206N-[3-cyano-5-cyclopropyl-2-(4-fluorophenyl)-1-benzofuran-6-yl]methanesulfonamide

生成物 1

HCID 679813243-{[3-Cyano-5-cyclopropyl-2-(4-fluorophenyl)-1-benzofuran-6-yl](methylsulfonyl)amino}propane-1-sulfonamide収率 64.3%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of Example 11A (0.150 g, 0.405 mmol) in dry dimethyl sulfoxide (1.3 mL) under a nitrogen atmosphere was treated with potassium carbonate (0.090 g, 0.648 mmol), and the bright yellow mixture was stirred at room temperature for 30 minutes. Then 3-chloropropane-1-sulfonamide (0.096 g, 0.607 mmol) and sodium iodide (0.091 g, 0.607 mmol) were added, and the resultant mixture was heated at 50° C. for 22 hours. Additional potassium carbonate (0.090 g, 0.648 mmol), 3-chloropropane-1-sulfonamide (0.096 g, 0.607 mmol) and sodium iodide (0.091 g, 0.607 mmol) were added and stirring was continued at 50° C. for 23 hours. The reaction was incomplete by LCMS, so additional potassium carbonate (0.090 g, 0.648 mmol), 3-chloropropane-1-sulfonamide (0.096 g, 0.607 mmol) and sodium iodide (0.091 g, 0.607 mmol) were added followed by continued stirring at 50° C. for 22 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL), and washed with water (3×25 mL) and brine (10 mL). The organic phase was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. Purification by silica gel flash chromatography (10 g) eluting with 3% methanol/dichloromethane followed by trituration with diethyl ether (3×5 mL) afforded the title compound as white solid (0.128 g, 64%). MS (ESI+) m/z 509 (M+NH4)+, (ESI−) m/z 490 (M−H)−.

後処理

  1. stirringstirring
  2. waitwas continued at 50° C. for 23 hours
  3. additionwere added
  4. stirringby continued stirring at 50° C. for 22 hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. washwashed with water (3×25 mL) and brine (10 mL)
  7. dry with materialThe organic phase was dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel flash chromatography (10 g)
  11. washeluting with 3% methanol/dichloromethane

出典と根拠

ORDレコード
ord-0fd3bb2a42814e95b8280ed75170940c
出典データセット
uspto-grants-2015_11
特許番号
US09173887B2

反応ノート

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