Triethylamine → 3-{1-[5-(6-Bromopyridin-2-yl)-thiazol-2-yl]piperidin-4-yl}propionic acid methyl ester

HRID 1716522Notes

Reaction equation

HRID 1716522 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8]Cl)[N:3]=1.[CH3:10][O:11][C:12](=[O:24])[CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21](=[S:23])[NH2:22])[CH2:17][CH2:16]1.[CH3:25]OC(OC)N(C)C.C(N(CC)CC)C>C(O)C>[CH3:10][O:11][C:12](=[O:24])[CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]2[S:23][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[N:3]=3)=[CH:25][N:22]=2)[CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 78373Dimethylformamide dimethyl acetalHCID 216984342-Bromo-6-(chloromethyl)pyridineHCID 451186894-Piperidinepropanoic acid,1-(aminothioxomethyl)-,methyl ester

Product 1

HCID 587064873-{1-[5-(6-Bromopyridin-2-yl)-thiazol-2-yl]piperidin-4-yl}propionic acid methyl esterYield 164.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To an solution of 2-bromo-6-chloromethylpyridine (1.88 g, 1.11 mmol) obtained in Step 1 of Example 1 in ethanol (20 ml), 3-(1-thiocarbamoylpiperidin-4-yl)propionic acid methyl ester (2.10 g, 9.12 mmol) obtained in Step 1 was added and the mixture was heated at reflux overnight. The reaction solution was cooled to room temperature, dimethylformamide dimethylacetal (1.8 ml, 14 mmol) and triethylamine (3.8 ml, 27 mmol) were added, and heated at reflux for 1 hour. After the reaction solution was concentrated, water was added, and it 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=50:50 to 0:100) and the title compound (748 mg, 20%) was obtained.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux overnight
  3. temperatureheated
  4. temperatureat reflux for 1 hour
  5. concentrationAfter the reaction solution was concentrated
  6. additionwater was added
  7. extractionit 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=50:50 to 0:100)

Sources & evidence

ORD record
ord-47bc38572a3e4029962996a8e3a5ac1d
Source dataset
uspto-grants-2010_09
Patent number
US07803801B2

Reaction notes

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