Ethyl 2-bromo-1,3-thiazole-4-carboxylate → Ethyl 2-(4-{[(4-bromo-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-1,3-thiazole-4-carboxylate

HRID 2233964Notes

Reaction equation

HRID 2233964 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[C:5]([C:9]([NH:11][CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[O:10])[NH:6][C:7]=1[CH3:8].C(=O)(O)[O-].[Na+].Br[C:24]1[S:25][CH:26]=[C:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:28]=1>CN(C=O)C.CCOC(C)=O.O>[Br:2][C:3]1[CH:4]=[C:5]([C:9]([NH:11][CH:12]2[CH2:13][CH2:14][N:15]([C:24]3[S:25][CH:26]=[C:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:28]=3)[CH2:16][CH2:17]2)=[O:10])[NH:6][C:7]=1[CH3:8]

Participants

7

Reactant 3

HCID 353965Ethyl 2-bromo-1,3-thiazole-4-carboxylateHCID 516892Sodium BicarbonateHCID 68579819HCID 68579819, compound2×

Product 1

HCID 68579941Ethyl 2-(4-{[(4-bromo-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)-1,3-thiazole-4-carboxylateYield 49.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

4-Bromo-5-methyl-N-piperidin-4-yl-1H-pyrrole-2-carboxamide hydrochloride (intermediate 57, 0.41 g, 1.27 mmol), sodium bicarbonate (0.42 g, 1.78 mmol) and ethyl 2-bromo-1,3-thiazole-4-carboxylate (0.30 g, 1.27 mmol) were combined in DMF (5 ml) under nitrogen and heated at 50° C. for 18 h. The mixture was cooled to room temperature and diluted with EtOAc (75 ml) and water (10 ml). The organic layer was separated, dried over sodium sulphate, filtered and concentrated under vacuum. Purification by flash chromatography (MeOH/DCM, 10%) provided 275 mg of the title compound.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customPurification by flash chromatography (MeOH/DCM, 10%)

Sources & evidence

ORD record
ord-4acfe271a4134d418f2e29eb0057fad8
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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