3,4-dihydro-2H-pyran → 3-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridine

HRID 1047266ノート

反応式

HRID 1047266 の反応式
[Br:1][C:2]1[C:3]([CH3:13])=[N:4][C:5]([C:8]2[N:12]=[CH:11][NH:10][N:9]=2)=[CH:6][CH:7]=1.[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1>O1CCCC1.C(OCC)(=O)C.CCCCCC.C(O)(C(F)(F)F)=O>[Br:1][C:2]1[C:3]([CH3:13])=[N:4][C:5]([C:8]2[N:12]=[CH:11][N:10]([CH:15]3[CH2:16][CH2:17][CH2:18][CH2:19][O:14]3)[N:9]=2)=[CH:6][CH:7]=1

参加物

7

反応物 2

HCID 80803,4-dihydro-2H-pyranHCID 178432644HCID 178432644、化合物

生成物 1

HCID 582983093-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridine収率 42%

試薬・触媒・溶媒 4

HCID 6422Trifluoroacetic acid触媒HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
70 °C

実験手順

3-Bromo-2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridine (0.7 g, 2.93 mmol) and 3,4-dihydro-2H-pyran (0.493 g, 5.86 mmol) were dissolved in tetrahydrofuran (20 mL). TFA (3.34 mg, 0.029 mmol) was added and the resulting solution was heated to 70° C. for 16 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, filtered and poured into a separatory funnel containing water and ethyl acetate. The organic layer was concentrated under reduced pressure. Flash chromatography (0-60% ethyl acetate in hexane) gave the desired product as a white solid (0.40 g, 1.23 mmol, 42% yield). MS (ESI) m/z 325.1 [M+2]+. Alternate approach: 3-Bromo-2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridine (1 equiv), 3,4-dihydro-2H-pyran (2 equiv) and methanesulfonic acid (0.08 equiv) were combined in tetrahydrofuran (8×vol). The solution was heated and stirred at 68° C. for 3.5 h then cooled to room temperature. Triethylamine (0.4 equiv) was added and the resulting solution was concentrated under reduced pressure to an oil. The oil was treated with acetonitrile and concentrated under reduced pressure iteratively until a solid was obtained. The solid was dissolved in acetonitrile and treated with water. The suspension was filtered and the solids were collected and dried. The crude product was slurried in hexanes, filtered and dried to give the purified title compound as a light pink solid.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. additionpoured into a separatory funnel
  4. additioncontaining water and ethyl acetate
  5. concentrationThe organic layer was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-de82fdcda4b145389eca83e75e89de76
出典データセット
uspto-grants-2013_10
特許番号
US08569494B2

反応ノート

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