Diisopropylethylamine → 4-Amino-1-(5-methanesulfonyl-2-pyridyl)-4-methylpiperidine

HRID 855896Notes

Reaction equation

HRID 855896 reaction equation
Cl.C(OC(=O)[NH:11][C:12]1([CH3:18])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)C1C=CC=CC=1.Br[C:21]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][N:22]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[CH3:30][S:27]([C:24]1[CH:25]=[CH:26][C:21]([N:15]2[CH2:14][CH2:13][C:12]([NH2:11])([CH3:18])[CH2:17][CH2:16]2)=[N:22][CH:23]=1)(=[O:29])=[O:28]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 98994832-Bromo-5-(methylsulfonyl)pyridineHCID 24728615Benzyl (4-methylpiperidin-4-yl)carbamate hydrochloride

Product 1

HCID 178609824-Amino-1-(5-methanesulfonyl-2-pyridyl)-4-methylpiperidineYield 72.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of (4-methyl-piperidin-4-yl)-carbamic acid benzyl ester hydrochloride salt (0.37 g, 1.3 mmol, Example 30B), 2-bromo-5-(methylsulfonyl)pyridine (0.27 g, 1.15 mmol) and diisopropylethylamine (0.7 mL) in dioxane (4 mL) in a sealed tube was heated to 80° C. for 16 hours. The mixture was cooled, concentrated under reduced pressure and purified by chromatography (silica gel, eluting with 5% hexane/ethyl acetate to 25% ethyl acetate/hexane) to provide the titled compound (0.225 g) as a white solid. MS (CI) m/z 404 (M+1)+; 1H NMR (300 MHz, CDCl3) δ ppm 8.63 (d, 1H), 7.86 (dd, 1H), 7.37 (m, 5H), 6.65 (d, 1H), 5.07 (s, 2H), 4.67 (s, 1H), 4.04-3.96 (m, 2H), 3.49-3.39 (m, 2H), 3.03 (s, 3H), 2.19-2.12 (m, 2H), 1.71-1.61 (m, 2H), 1.41 (s, 3H).

Workup

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. custompurified by chromatography (silica gel, eluting with 5% hexane/ethyl acetate to 25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-c7554e71a24342759a327a3e1620561c
Source dataset
uspto-grants-2007_08
Patent number
US07262207B2

Reaction notes

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