Triethylamine → N-[5-Bromo-4-methyl-3-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-2-(4-methanesulfonyl-phenyl)-acetamide

HRID 1497760ノート

反応式

HRID 1497760 の反応式
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([OH:14])=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(Cl)(=O)C(Cl)=O.[Br:21][C:22]1[C:23]([CH3:39])=[C:24]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=2)[C:25]([NH2:28])=[N:26][CH:27]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[Br:21][C:22]1[C:23]([CH3:39])=[C:24]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:36])[F:37])[CH:30]=2)[C:25]([NH:28][C:12](=[O:14])[CH2:11][C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][CH:9]=2)=[N:26][CH:27]=1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 5723454-Mesylphenylacetic acidHCID 867080865-Bromo-4-methyl-3-(3-trifluoromethyl-phenyl)-pyridin-2-ylamine

生成物 1

HCID 86708096N-[5-Bromo-4-methyl-3-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-2-(4-methanesulfonyl-phenyl)-acetamide収率 38.7%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒2 回

実験手順

To a suspension of 4-(methylsulfonyl)phenylacetic acid (388 mg, 1.8 mmol) in dry DCM (5 mL) was added oxalyl chloride (320 μL, 3.6 mmol) followed by DMF (2 drops). The reaction mixture was stirred at RT for 3 hrs then the solvent was removed in vacuo. The resultant residue was taken up in DCM (2 mL) and added dropwise to a stirring solution of 5-bromo-4-methyl-3-(3-trifluoromethyl-phenyl)-pyridin-2-ylamine (Int. 1, 500 mg, 1.51 mmol) and triethylamine (420 μL, 36.02 mmol) in DCM (2 mL) at 0-5° C. The reaction mixture was stirred at 0-5° C. for 3 hrs then gradually warmed to RT over 5 hrs. The reaction mixture was partitioned between saturated sodium hydrogen carbonate solution and DCM. The organic phase was concentrated in vacuo and purified by flash chromatography eluting with a gradient of 0-100% EtOAc in cyclohexane to give the title compound as an orange glass (308 mg).

後処理

  1. customthe solvent was removed in vacuo
  2. stirringThe reaction mixture was stirred at 0-5° C. for 3 hrs
  3. temperaturethen gradually warmed to RT over 5 hrs
  4. customThe reaction mixture was partitioned between saturated sodium hydrogen carbonate solution and DCM
  5. concentrationThe organic phase was concentrated in vacuo
  6. custompurified by flash chromatography
  7. washeluting with a gradient of 0-100% EtOAc in cyclohexane

出典と根拠

ORDレコード
ord-add18c11b1fe4eefb29cbccfebed49cf
出典データセット
uspto-grants-2015_12
特許番号
US09199984B2

反応ノート

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