Hexachloroethane → 6-Fluoro-3-(2-pyrrolidin-1-yl-ethyl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 1402079Notes

Reaction equation

HRID 1402079 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10](=O)[CH2:11][CH2:12][N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[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>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([CH2:11][CH2:12][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[N:9][N:8]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 866869443-Pyrrolidin-1-yl-propionic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

Product 1

HCID 866869456-Fluoro-3-(2-pyrrolidin-1-yl-ethyl)-[1,2,4]triazolo[4,3-a]pyridineYield 73.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Intermediate 1a (400 mg) was dissolved in THF (20 mL) and cooled in an ice/water bath. Triphenylphosphine (643 mg, 2.45 mmol) was added followed by triethylamine (682 μL, 4.90 mmol) and hexachloroethane (581 mg, 2.45 mmol). The reaction mixture was stirred for 18 h and then loaded onto an SCX-2 cartridge, which was washed with MeOH then eluted with 2M NH3 in MeOH. The resulting residue was purified by FCC using 0-10% [2M NH3 in MeOH] in DCM to give the title compound (292 mg, 1.16 mmol, 52%). 1H NMR (400 MHz, CDCl3): 1.80-1.87 (4H, m), 2.60-2.68 (4H, m), 3.00-3.10 (2H, t, J 7.3), 3.24-3.34 (2H, t, J 7.3), 7.13-7.21 (1H, ddd, J 9.9, 7.6, 2.3), 7.70-7.77 (1H, dd, J 9.8, 4.5), 8.00-8.04 (1H, m).

Workup

  1. temperaturecooled in an ice/water bath
  2. washwas washed with MeOH
  3. washthen eluted with 2M NH3 in MeOH
  4. customThe resulting residue was purified by FCC

Sources & evidence

ORD record
ord-98702712afa74d5e9ca3363d6ea2c88a
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

Loading…