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

HRID 2285036Notes

Reaction equation

HRID 2285036 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10]([C@@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2[CH2:17][CH3:18])=O)=[N:6][CH:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.ClC(Cl)(Cl)C(Cl)(Cl)Cl.N>C1COCC1.CO.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:10]([C@@H:12]3[CH2:16][CH2:15][CH2:14][N:13]3[CH2:17][CH3:18])=[N:9][N:8]=2)[CH:7]=1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 117665886(S)-1-Ethyl-pyrrolidine-2-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

Product 1

HCID 896125566-Fluoro-3-((S)-1-ethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridineYield 89.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Intermediate 61a (190 mg, 0.75 mmol), Ph3P (395 mg, 1.51 mmol) and Et3N (419 μL, 3.01 mmol) in THF (6.00 mL) at 0° C. was added hexachloroethane (357 mg, 1.51 mmol). The reaction was stirred at RT overnight then 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 dissolved in MeOH and loaded onto an SCX-2 cartridge, which was washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave a residue. FCC, using 0-10% [2M NH3 in MeOH] in DCM, gave the title compound (157 mg, 89%). LCMS (Method 2): Rt 0.28 min, m/z 235.2 [MH+].

Workup

  1. customthen partitioned between EtOAc and water
  2. extractionThe aqueous layer was then extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. dissolutionThe residue was dissolved in MeOH
  8. washwas washed with MeOH
  9. washThe product was eluted with 2M NH3 in MeOH
  10. concentrationconcentration in vacuo
  11. customgave a residue

Sources & evidence

ORD record
ord-47e4f50593254b0e9117dca0c4836542
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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