Potassium Carbonate → 2-((3-cyclopropyl-4-nitro-1H-indazol-1-yl)methyl)-5-methyl-1,3,4-thiadiazole

HRID 79458ノート

反応式

HRID 79458 の反応式
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]2[S:16][C:17]([CH3:20])=[N:18][N:19]=2)[N:3]=1.[CH:21]1(B(O)O)[CH2:23][CH2:22]1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=C(S([O-])(=O)=O)C=2OC)CCCCC1.[Na+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH:21]1([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][C:9]=3[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]3[S:16][C:17]([CH3:20])=[N:18][N:19]=3)[N:3]=2)[CH2:23][CH2:22]1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 23677046Sodium 2'-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonateHCID 672601402-((3-bromo-4-nitro-1H-indazol-1-yl)methyl)-5-methyl-1,3,4-thiadiazole

生成物 1

HCID 672590452-((3-cyclopropyl-4-nitro-1H-indazol-1-yl)methyl)-5-methyl-1,3,4-thiadiazole収率 15.5%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

A 10 mL round bottom flask equipped with a reflux condenser and a nitrogen line was charged with 2-((3-bromo-4-nitro-1H-indazol-1-yl)methyl)-5-methyl-1,3,4-thiadiazole (195 mg, 0.551 mmol), cyclopropylboronic acid (104 mg, 1.21 mmol), palladium acetate (7 mg, 0.031 mmol), potassium carbonate (258 mg, 1.87 mmol), and sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonate (32 mg, 0.062 mmol). To the flask was added a 1,4-dioxane:water mixture (5:1; 2.4 mL) and the flask was evacuated and refilled with nitrogen three times. The reaction mixture was heated at reflux for 8 hours followed by stirring for 16 hours at ambient temperature. The cooled reaction mixture was diluted with excess water and extracted multiple times with DCM and EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to preparative thin-layer chromatography (silica, 5% MeOH-DCM as eluent) to afford the desired product (27 mg) as a solid.

後処理

  1. customA 10 mL round bottom flask equipped with a reflux condenser
  2. customwater mixture (5:1; 2.4 mL) and the flask was evacuated
  3. additionrefilled with nitrogen three times
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux for 8 hours
  6. customThe cooled reaction mixture
  7. extractionextracted multiple times with DCM and EtOAc
  8. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-eb491b5e19914fa7962c0791bff0d362
出典データセット
uspto-grants-2014_09
特許番号
US08841455B2

反応ノート

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