1,2-Dichloroethane → 8-(3,4-Difluorophenyl)-N-(4-methyl-1-(6-methylpyrimidin-4-yl)piperidin-4-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 451551Notes

Reaction equation

HRID 451551 reaction equation
I.[CH3:2][C:3]1([NH:16][C:17](SC)=[NH:18])[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11][N:10]=2)[CH2:5][CH2:4]1.Cl[CH2:22][CH2:23][CH2:24][CH:25]([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=1)[C:26](O)=O.C(Cl)CCl.O.O[N:43]1C2C=CC=CC=2N=[N:44]1.CCN(C(C)C)C(C)C.NN>CN(C=O)C.O>[F:36][C:31]1[CH:30]=[C:29]([CH:25]2[CH2:24][CH2:23][CH2:22][N:43]3[N:44]=[C:17]([NH:16][C:3]4([CH3:2])[CH2:8][CH2:7][N:6]([C:9]5[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11][N:10]=5)[CH2:5][CH2:4]4)[N:18]=[C:26]23)[CH:34]=[CH:33][C:32]=1[F:35]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 673440915-Chloro-2-(3,4-difluorophenyl)pentanoic acidHCID 178504014HCID 178504014, compound

Product 1

HCID 583979268-(3,4-Difluorophenyl)-N-(4-methyl-1-(6-methylpyrimidin-4-yl)piperidin-4-yl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amineYield 1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 4-methyl-1-(6-methylpyrimidin-4-yl)piperidin-4-ylcarbamimidothioate hydroiodide (1.85, 4.54 mmol) containing 5-chloro-2-(3,4-difluorophenyl)pentanoic acid (1.24, 5.00 mmol), EDC (0.87, 4.54 mmol) and 1-hydroxybenzotriazole hydrate (1.39 g, 9.08 mmol) in DMF (22.3 mL) was added DIPEA (1.98 mL, 11.4 mmol) and the reaction mixture was stirred at room temperature for 18 hours. Hydrazine monoydrate (0.57 mL, 18.2 mmol) was then added and the reaction mixture stirred at 70° C. for 5 h. The reaction mixture was then poured into water, extracted twice with ethyl acetate, and the combined organic layers washed with brine, dried over sodium sulfate, filtered and evaporated. Purification by chromatography (silica gel, 2×50 g, 0 to 20% methanol in dichloromethane) afforded the title compound (14 mg, 1%) as a light red foam.

Workup

  1. stirringthe reaction mixture stirred at 70° C. for 5 h
  2. extractionextracted twice with ethyl acetate
  3. washthe combined organic layers washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by chromatography (silica gel, 2×50 g, 0 to 20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-4a2b8882ac3e4c6eb2087f77320e5271
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

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