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

HRID 2285144Notes

Reaction equation

HRID 2285144 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([C:10]([N:12]2[C@H:17]([CH3:18])[CH2:16][CH2:15][CH2:14][C@@H:13]2[CH3:19])=O)N)=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC[N:41](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:8]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]2=[N:6][N:41]=1

Participants

6

Reactant 4

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 117666126cis-2,6-Dimethyl-piperidine-1-carboxylic acid N-(5-fluoro-pyridin-2-yl)-hydrazide

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

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%). 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).

Workup

  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

Sources & evidence

ORD record
ord-934ece55a175490690c8cd4c15e9b692
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

Loading…