Hexachloroethane → HCID 67344430, compound

HRID 451564Notes

Reaction equation

HRID 451564 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([NH2:11])[N:10]=[C:4]2[CH:3]=1.ClC(Cl)(Cl)C(Cl)(Cl)Cl.C(N(CC)CC)C.CP(C)C.[CH3:31][C:32]1[N:36]=[C:35]([N:37]2[CH2:42][CH2:41][C:40](=O)[CH2:39][CH2:38]2)[S:34][N:33]=1.[B][B][B][B][B][B][B][B][B][B].C([O-])(O)=O.[Na+]>C1COCC1.CO>[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([NH:11][CH:40]3[CH2:39][CH2:38][N:37]([C:35]4[S:34][N:33]=[C:32]([CH3:31])[N:36]=4)[CH2:42][CH2:41]3)[N:10]=[C:4]2[CH:3]=1

Participants

10

Reactant 7

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 68983TrimethylphosphineHCID 516892Sodium BicarbonateHCID 545940257-Bromo[1,2,4]triazolo[1,5-a]pyridin-2-amineHCID 592585101-(3-Methyl-1,2,4-thiadiazol-5-yl)piperidin-4-oneHCID 178419135HCID 178419135, compound3×

Product 1

HCID 67344430HCID 67344430, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 7-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine (prepared in analogy to example 66a-b starting from 4-bromo-pyridin-2-ylamine) (250 mg, 1.17 mmol) and hexachloroethane (333 mg, 1.41 mmol) under argon in dry THF (12.5 mL) was added triethylamine (356 mg, 491 μL, 3.52 mmol) and the mixture was heated to 50° C. for 10 minutes. Trimethylphosphine (1 M in THF, 1.41 mL, 1.41 mmol) was added. The reaction mixture was stirred at room temperature for 0.5 h, then 1-(3-methyl-1,2,4-thiadiazol-5-yl)piperidin-4-one (278 mg, 1.41 mmol) was added and the mixture heated in the microwave to 150° C. for 30 minutes. To the reaction mixture a solution of decaborane (143 mg, 153 μL, 1.17 mmol) in dry methanol (3 mL) was added and stirred at for 3 hours at room temperature. Further decaborane (34.4 mg, 36.6 μL, 282 μmol) in dry methanol (1.00 mL) was added. The reaction mixture was heated to 60° C. for 12 hours. Further decaborane (17 mg) dissolved in methanol (1 mL) was added and heated to 70° C. for 3 hours. Aqueous NaHCO3 solution was added and the aqueous phase was extracted with CH2Cl2, the organic layers were combined, dried over Na2SO4, filtered and the solvents were evaporated. The residue was purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane). The title compound was obtained as off-white solid (300 mg, 65%).

Workup

  1. temperaturethe mixture heated in the microwave to 150° C. for 30 minutes
  2. stirringstirred at for 3 hours at room temperature
  3. temperatureThe reaction mixture was heated to 60° C. for 12 hours
  4. additionwas added
  5. temperatureheated to 70° C. for 3 hours
  6. extractionthe aqueous phase was extracted with CH2Cl2
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customthe solvents were evaporated
  10. customThe residue was purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane)

Sources & evidence

ORD record
ord-cff557ed5c944d6cadeece937dbba1d3
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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