Hexachloroethane → 3-Cyclohexyl-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine

HRID 572112Notes

Reaction equation

HRID 572112 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=O)=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.ClC(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1.O>[CH:12]1([C:10]2[N:6]3[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]3=[N:8][N:9]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86686727Cyclohexanecarboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

Product 1

HCID 866867283-Cyclohexyl-6-fluoro-[1,2,4]triazolo[4,3-a]pyridineYield 31.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Intermediate 34a (1.15 g, 4.83 mmol), triphenylphosphine (2.54 g, 9.67 mmol), and triethylamine (2.68 mL, 19.3 mmol) in dry THF (17 mL) at 0° C. under N2 was added hexachloroethane (2.28 g, 9.67 mmol), and the mixture stirred at 0° C. for 15 min, and at RT for 6 h. Water was added, then the organics washed with brine, dried (MgSO4) and concentrated in vacuo. Flash chromatography (silica gel, 0-100% EtOAc in cyclohexane) gave the title compound as an off-white solid (330 mg, 31%). 1H NMR (400 MHz, CDCl3): 1.36-1.55 (3H, m), 1.78-2.00 (5H, m), 2.05-2.14 (2H, m), 2.97 (1H, tt, J=11.5, 3.5 Hz), 7.16 (1H, ddd, J=10.0, 7.5, 2.3 Hz), 7.76 (1H, dd, J=10.0, 4.9, 0.9 Hz), 7.85 (1H, ddd, J=3.5, 2.2, 0.9 Hz).

Workup

  1. waitat RT for 6 h
  2. washthe organics washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d58f984e55e3458c9dfe36b7e18ec779
Source dataset
uspto-grants-2015_05
Patent number
US09029373B2

Reaction notes

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