Triethylamine → 2-{1-[5-(6-Bromopyridin-2-yl)thiazol-2-yl]piperidin-4-yl}-2-methylpropionic acid ethyl ester

HRID 1716526Notes

Reaction equation

HRID 1716526 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8]Cl)[N:3]=1.[CH2:10]([O:12][C:13](=[O:26])[C:14]([CH3:25])([CH:16]1[CH2:21][CH2:20][N:19]([C:22](=[S:24])[NH2:23])[CH2:18][CH2:17]1)[CH3:15])[CH3:11].[CH3:27]OC(OC)N(C)C.C(N(CC)CC)C>C(O)C>[CH2:10]([O:12][C:13](=[O:26])[C:14]([CH:16]1[CH2:17][CH2:18][N:19]([C:22]2[S:24][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[N:3]=3)=[CH:27][N:23]=2)[CH2:20][CH2:21]1)([CH3:25])[CH3:15])[CH3:11]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 78373Dimethylformamide dimethyl acetalHCID 216984342-Bromo-6-(chloromethyl)pyridineHCID 587067252-Methyl-2-(1-thiocarbamoylpiperidin-4-yl)propionic acid ethyl ester

Product 1

HCID 587068292-{1-[5-(6-Bromopyridin-2-yl)thiazol-2-yl]piperidin-4-yl}-2-methylpropionic acid ethyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2-bromo-6-chloromethylpyridine (2.14 g, 10.4 mmol) obtained in Step 1 of Example 1 in ethanol (30 ml), 2-methyl-2-(1-thiocarbamoylpiperidin-4-yl)propionic acid ethyl ester (2.44 g, 9.43 mmol) obtained in Step 1 was added and the mixture was heated at reflux for 5 hours. The reaction solution was cooled to room temperature, dimethylformamide dimethylacetal (1.9 ml, 14 mmol) and triethylamine (3.9 ml, 28 mmol) were added, and heated at reflux for 1 hour. After the reaction solution was concentrated, water was added, and the solution was extracted with ethyl acetate and washed with a saturated brine. The organic layer was dried over magnesium sulfate and the residue obtained by vacuum concentration was purified by chromatography on silica gel (n-hexane:ethyl acetate=2:1 to 1:1) and the title compound (2.48 g, 60%) was obtained.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 5 hours
  3. temperatureheated
  4. temperatureat reflux for 1 hour
  5. concentrationAfter the reaction solution was concentrated
  6. additionwater was added
  7. extractionthe solution was extracted with ethyl acetate
  8. washwashed with a saturated brine
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. customthe residue obtained by vacuum concentration
  11. customwas purified by chromatography on silica gel (n-hexane:ethyl acetate=2:1 to 1:1)

Sources & evidence

ORD record
ord-887a403b862d4b2d9f63c88def4d453d
Source dataset
uspto-grants-2010_09
Patent number
US07803801B2

Reaction notes

Loading…