Triethylamine → 1-(t-Butoxycarbonyl)-4-([1,2,4]triazolo[4,3-a]pyridin-3-yl)piperidine

HRID 1068227Notes

Reaction equation

HRID 1068227 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH:16][NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClP(Cl)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCN(CC)CC>CC#N.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]3=[N:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 260420Triphenylphosphine dichlorideHCID 211930971-(t-Butoxycarbonyl)-4-(2-(2-pyridinyl)hydrazino)carbonyl-piperidine

Product 1

HCID 69172981-(t-Butoxycarbonyl)-4-([1,2,4]triazolo[4,3-a]pyridin-3-yl)piperidineYield 59.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(t-butoxycarbonyl)-4-(2-(2-pyridinyl)hydrazino)carbonyl-piperidine (320 mg, 1.0 mmol) and dichlorotriphenylphosphorane (666 mg, 2.1 mmol) in CH3CN (10 mL) was added Et3N (0.42 mL, 3.0 mmol). After refluxing for 2h, the solution was diluted with EtOAc. The aqueous layer was extracted with EtOAc (3×). Combined organic phase was washed with brine and dried over anhydrous MgSO4. Concentration followed by flash chromatography eluting with 100% EtOAc, then 10% MeOH/CH2Cl2 afforded the title compound (180 mg) as a foamy solid. 1H NMR (500 MHz, CDCl3): δ 1.50 (s, 9H), 2.05˜2.11 (m, 4H), 3.03 (br s, 2H), 3.24 (m, 1H), 4.25 (br d, J=11.7 Hz, 1H), 6.86 (dt, J=6.9, 0.9 Hz, 1H), 7.25 (m, 1H), 7.78 (dt, J=9.4, 1.2 Hz, 1H), 7.95 (dt, J=6.8, 1.1 Hz, 1H), 7.79 (dd, J=7.3, 0.8 Hz, 1H).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (3×)
  2. washCombined organic phase was washed with brine
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationConcentration
  5. washeluting with 100% EtOAc

Sources & evidence

ORD record
ord-fb4dd47d2c8e43a2ac9ed1451ede93c0
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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