Diisopropylethylamine → 4-(5-Methanesulfonyl-pyridin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 2355618Notes

Reaction equation

HRID 2355618 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][N:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(N(C(C)C)C(C)C)C>C(#N)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:25][C:2]2[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][N:3]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 98994832-Bromo-5-(methylsulfonyl)pyridine

Product 1

HCID 674012504-(5-Methanesulfonyl-pyridin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl esterYield 70.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 2-bromo-5-methanesulfonyl-pyridine (0.24 g, 1.0 mmol, 1.0 equiv; prepared as described in EP 1298 116 A1 (Pfizer Products Inc., USA)) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (0.23 g, 1.1 mmol, 1.1 equiv) in acetonitrile (6.0 mL) was added N-ethyl diisopropylamine (0.87 mL, 0.66 g, 5.0 mmol, 5.0 equiv) drop by drop at rt and the reaction mixture heated to reflux for 19 h. The reaction mixture was poured into crashed ice and extracted twice with ethyl acetate. The combined organic layers were washed with brine and water, dried over MgSO4, filtered and concentrated by evaporation under reduced pressure. The crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol to give 0.25 g (70%) of the title compound as light brown oil. MS (ISP): 356.1 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureto reflux for 19 h
  3. additionThe reaction mixture was poured
  4. extractionextracted twice with ethyl acetate
  5. washThe combined organic layers were washed with brine and water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated by evaporation under reduced pressure
  9. customThe crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol

Sources & evidence

ORD record
ord-83d3f3137c334994914a19b998646969
Source dataset
uspto-grants-2010_07
Patent number
US07754744B2

Reaction notes

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