Triethylamine → 3-bromo-6-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-2-fluorobenzamide

HRID 522133ノート

反応式

HRID 522133 の反応式
[Br:1][C:2]1[C:3]([F:12])=[C:4]([C:8]([Cl:11])=[CH:9][CH:10]=1)[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[N:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:23]=[C:22]([C:31]#[N:32])[CH:21]=1.C(N(CC)CC)C.[OH-].[Na+]>C(Cl)Cl.CN(C=O)C.CC#N>[Br:1][C:2]1[C:3]([F:12])=[C:4]([C:8]([Cl:11])=[CH:9][CH:10]=1)[C:5]([NH:19][C:20]1[N:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:23]=[C:22]([C:31]#[N:32])[CH:21]=1)=[O:7]

参加物

9

反応物 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 17763654HCID 17763654、化合物HCID 217423273-Bromo-6-chloro-2-fluorobenzoic acid

生成物 1

HCID 1184971903-bromo-6-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-2-fluorobenzamide収率 13.4%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 3-bromo-6-chloro-2-fluorobenzoic acid (1 g, 3.95 mmol) in DCM (20 mL) was added DMF (1 drop) followed by oxalyl chloride (0.7 mL, 7.89 mmol) dropwise. The reaction was stirred at room temperature for 30 minutes before concentrating in vacuo and azeotroping with DCM. The residue was dissolved in MeCN (5 mL) and 5-amino-1-phenyl-1H-pyrazole-3-carbonitrile (655 mg, 3.56 mmol) and triethylamine (0.55 mL, 3.95 mmol) in MeCN (7 mL) were added. The reaction was heated at 120° C. for 1 hour under microwave irradiation. 2M NaOH (aq) (20 mL) was added with vigorous stirring at room temperature for 1.5 hours. The organic layer was separated, washed with 2M HCl (aq) (2×20 mL), dried over magnesium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 10-30% EtOAc in heptanes to afford the title compound (200 mg, 13%).

後処理

  1. concentrationbefore concentrating in vacuo
  2. customazeotroping with DCM
  3. dissolutionThe residue was dissolved in MeCN (5 mL)
  4. temperatureThe reaction was heated at 120° C. for 1 hour under microwave irradiation
  5. stirringwith vigorous stirring at room temperature for 1.5 hours
  6. customThe organic layer was separated
  7. washwashed with 2M HCl (aq) (2×20 mL)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with 10-30% EtOAc in heptanes

出典と根拠

ORDレコード
ord-93a2a903959b4e6ea342aed2b7e5220e
出典データセット
uspto-grants-2016_05
特許番号
US09328096B2

反応ノート

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