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

HRID 717199노트

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HRID 717199 반응식
[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.CS(O)(=O)=O>O1CCCC1>[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

참가 물질

5

반응물 3

HCID 6395Methanesulfonic AcidHCID 80803,4-dihydro-2H-pyranHCID 178432644HCID 178432644, 화합물

생성물 1

HCID 582983093-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridine수율 85.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
65 °C

실험 절차

To a suspension of 3-bromo-2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridine (96.0 g, 0.4 mol) in tetrahydrofuran (780 mL) was added 3,4-dihydro-2H-pyran (72.5 mL, 0.8 mol) and methanesulfonic acid (3.2 mL). The mixture was heated to 65° C. and the resulting yellow solution was allowed to stir at 65° C. for 6 h. The mixture was cooled to ambient temperature, quenched with triethylamine (23 mL), concentrated under reduced pressure and further dried in a high vacuum for 1 h. The resulting oil was dissolved in acetonitrile (250 mL) and the solution was added into water (750 mL) while stirring vigorously. More acetonitrile (80 mL) was added and the mixture was allowed to stir for 1 h. The resulting solids were filtered, washed with 1:4 acetonitrile/water (800 mL) and dried in a vacuum oven for 48 h to afford the product (110 g, 85% yield) as a white solid. The product was further purified by silica gel plug purification (1:1 hexanes/ethyl acetate) to give 88 g of the pure product as a white solid and 16.2 g of less pure product. MS (ESI) m/z 239.1 [M]+, 241.1 [M+2]+.

후처리

  1. temperatureThe mixture was cooled to ambient temperature
  2. customquenched with triethylamine (23 mL)
  3. concentrationconcentrated under reduced pressure
  4. customfurther dried in a high vacuum for 1 h
  5. dissolutionThe resulting oil was dissolved in acetonitrile (250 mL)
  6. additionthe solution was added into water (750 mL)
  7. stirringwhile stirring vigorously
  8. additionMore acetonitrile (80 mL) was added
  9. stirringto stir for 1 h
  10. filtrationThe resulting solids were filtered
  11. washwashed with 1:4 acetonitrile/water (800 mL)
  12. customdried in a vacuum oven for 48 h

출처 및 근거

ORD 기록
ord-a76e5c65f5ba42eaadd8423c951205a4
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193692B2

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