Hexachloroethane → 3-(4-Aza-spiro[2.5]oct-4-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridine

HRID 2285251Notes

Reaction equation

HRID 2285251 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:10]([N:12]2[CH2:19][CH2:18][CH2:17][CH2:16][C:13]32[CH2:15][CH2:14]3)=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>O1CCOCC1>[CH2:15]1[C:13]2([CH2:16][CH2:17][CH2:18][CH2:19][N:12]2[C:10]2[N:6]3[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]3=[N:8][N:9]=2)[CH2:14]1

Participants

6

Reactant 4

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 866872644-Aza-spiro[2,5]octane-4-carboxylic acid N'-(5-fluoro-pyridin-2-yl)-hydrazide

Product 1

HCID 866872653-(4-Aza-spiro[2.5]oct-4-yl)-6-fluoro-[1,2,4]triazolo[4,3-a]pyridineYield 82%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of Intermediate 148b (587 mg, 2.22 mmol), triphenyl phosphine (1.17 g, 4.44 mmol) and triethylamine (1.24 mL, 8.88 mmol) in dioxane (25 mL) at RT was added hexachloroethane (1.05 g, 4.44 mmol). The resulting opaque solution was stirred at RT for 30 min, and at reflux for 16 h. The cooled solution was filtered, and the filter-cake washed with THF (5 mL). The combined organics were applied to an SCX-2 cartridge, which was washed with MeOH (100 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo left a brown oil. Flash chromatography (silica 40 g, 1.5-4.5% MeOH in DCM) gave the title compound as a brown gum (82%). LCMS (Method 3): Rt 2.92 min, m/z 247 [MH+].

Workup

  1. temperatureat reflux for 16 h
  2. filtrationThe cooled solution was filtered
  3. washthe filter-cake washed with THF (5 mL)
  4. washwas washed with MeOH (100 mL)
  5. washThe product was eluted with 2M NH3 in MeOH (75 mL)
  6. concentrationconcentration in vacuo
  7. waitleft a brown oil

Sources & evidence

ORD record
ord-2b1d9037a8fd4ba5a527b36186e12c6f
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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