Hexachloroethane → 3-(cis-2,6-Dimethyl-piperidin-1-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine

HRID 630863노트

반응식

HRID 630863 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10]([N:12]2[C@H:17]([CH3:18])[CH2:16][CH2:15][CH2:14][C@@H:13]2[CH3:19])=O)=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCN(CC)CC.ClC(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[CH3:19][C@H:13]1[CH2:14][CH2:15][CH2:16][C@@H:17]([CH3:18])[N:12]1[C:10]1[N:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]2=[N:8][N:9]=1

참가 물질

6

반응물 4

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86687154cis-2,6-Dimethyl-piperidine-1-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

생성물 1

HCID 896242853-(cis-2,6-Dimethyl-piperidin-1-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine수율 80%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
55 °C

실험 절차

To an ice cold solution of Intermediate 96a (1.38 g, 5.19 mmol) in THF (50.0 mL) was added sequentially triphenylphosphine (2.72 g, 10.4 mmol), Et3N (2.89 mL, 20.8 mmol) and hexachloroethane (2.46 g, 10.4 mmol). The cooling bath was removed and the reaction was heated to 55° C. overnight. The reaction was cooled and partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was taken up in MeOH and loaded onto an SCX-2 cartridge, which was washed with MeOH and eluted with 2M NH3 in MeOH. The residue was concentrated in vacuo then resubmitted to the reaction conditions overnight. After analogous workup the residue was concentrated in vacuo to give the title compound (1.03 g, 80%). 1H NMR (300 MHz, CDCl3): 0.68 (6H, d, J 6.2 Hz), 1.36-1.68 (3H m), 1.74-1.90 (3H, m), 3.35 (2H, m), 7.14 (1H, ddd, J 9.8, 7.5, 2.3 Hz), 7.65 (1H, ddd, J 9.9, 4.7, 0.8 Hz), 8.02 (1H, ddd, J 3.2, 2.3, 0.8 Hz).

후처리

  1. customThe cooling bath was removed
  2. temperatureThe reaction was cooled
  3. custompartitioned between EtOAc and water
  4. extractionThe aqueous layer was then extracted with EtOAc (3×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. washwas washed with MeOH
  10. washeluted with 2M NH3 in MeOH
  11. concentrationThe residue was concentrated in vacuo
  12. customthen resubmitted to the reaction conditions overnight
  13. concentrationAfter analogous workup the residue was concentrated in vacuo

출처 및 근거

ORD 기록
ord-903ec086f1b64267938b51f067a3fb1d
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315503B2

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