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Ethanol → [8-(3,4-Difluoro-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[1-(5-methyl-[1,3,4]oxadiazol-2-yl)-piperidin-4-yl]-amine

HRID 451474
Notes
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Reaction equation

HRID 451474 reaction equation
[CH3:1][C:2]1[O:6][C:5]([N:7]2[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)=[N:4][N:3]=1.[F:14][C:15]1[CH:16]=[C:17]([CH:22]2[CH2:27][CH2:26][CH2:25][N:24]3[N:28]=[C:29]([NH2:31])[N:30]=[C:23]23)[CH:18]=[CH:19][C:20]=1[F:21].C(O)C.[BH4-].[Na+]>C1(C)C=CC=CC=1.C(O)(=O)C.O>[F:14][C:15]1[CH:16]=[C:17]([CH:22]2[CH2:27][CH2:26][CH2:25][N:24]3[N:28]=[C:29]([NH:31][CH:10]4[CH2:11][CH2:12][N:7]([C:5]5[O:6][C:2]([CH3:1])=[N:3][N:4]=5)[CH2:8][CH2:9]4)[N:30]=[C:23]23)[CH:18]=[CH:19][C:20]=1[F:21]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 702EthanolHCID 4311764Sodium borohydride2×HCID 583978531-(5-Methyl-[1,3,4]oxadiazol-2-yl)-piperidin-4-oneHCID 673426828-(3,4-Difluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Product 1

HCID 58397875[8-(3,4-Difluoro-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[1-(5-methyl-[1,3,4]oxadiazol-2-yl)-piperidin-4-yl]-amine

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 1-(5-methyl-1,3,4-oxadiazol-2-yl)piperidin-4-one (79.6 mg, 440 μmol) and 8-(3,4-difluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amine (110 mg, 440 mmol) in toluene (5 mL) and acetic acid (280 μL) was heated to reflux at a Dean-Stark trap. The reaction mixture was cooled to room temperature and ethanol (3 mL) was added followed by sodium borohydride (66.5 mg, 61.9 μL, 1.76 mmol). The reaction mixture was stirred at 50° C. for 3 hours. Further sodium borohydride (66.5 mg, 61.9 μL, 1.76 mmol) was added and stirred at 50° C. for 3 hours. Water was added to the reaction mixture and the aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, 100 g, 0% to 15% MeOH in dichloromethane, 40 minutes). The title compound was obtained as a white solid (32.8 mg, 18%). MS ISP (m/e): 416.3 (69) [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.16-7.07 (m, 1H), 7.00-6.93 (m, 1H), 6.91-6.87 (m, 1H), 4.12-4.01 (m, 4H), 3.93-3.87 (m, 2H), 3.72-3.60 (m, 1H), 3.23-3.13 (m, 2H), 2.38 (s, 3H), 2.32-2.23 (m, 1H), 2.18-1.88 (m, 5H), 1.58-1.48 (m, 2H).

Workup

  1. temperatureto reflux at a Dean-Stark trap
  2. stirringstirred at 50° C. for 3 hours
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. customthe solvent was evaporated
  6. customThe residue was purified by flash chromatography (silica gel, 100 g, 0% to 15% MeOH in dichloromethane, 40 minutes)

Sources & evidence

ORD record
ord-7e82613b6a2a4070813f87331fc4c022
Source dataset
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08486967B2

Reaction notes

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