Sodium hydride → 5-(2-diethylamino-ethyl)-3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

HRID 1811340Notes

Reaction equation

HRID 1811340 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:14][C:13]2[CH2:12][CH2:11][NH:10][C:9](=[O:15])[C:8]=2[C:7]=1[C:16]([F:19])([F:18])[F:17])=[O:5])[CH3:2].[H-].[Na+].Br.Br[CH2:24][CH2:25][N:26]([CH2:29][CH3:30])[CH2:27][CH3:28]>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[NH:14][C:13]2[CH2:12][CH2:11][N:10]([CH2:24][CH2:25][N:26]([CH2:29][CH3:30])[CH2:27][CH3:28])[C:9](=[O:15])[C:8]=2[C:7]=1[C:16]([F:18])([F:19])[F:17])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 706072-Bromoethyldiethylammonium bromideHCID 666086723-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 666084425-(2-diethylamino-ethyl)-3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl esterYield 28.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A stirred mixture of 3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (2.6 g, 9.4 mmol) in 40 ml of N,N-dimethylformamide was cooled down to 0° C. in an ice-water bath, added with sodium hydride slowly. Upon the completion of the addition, the reaction mixture was cooled down to −30˜40° C. and added with (2-bromo-ethyl)-diethyl-amine hydrobromide (2.95 g, 11.3 mmol) in 15 ml of N,N-dimethylformamide. The reaction mixture was stirred at room temperature overnight and extracted with saturated sodium chloride (100 ml) and dichloromethane (100 ml). The combined organic phase was washed with saturated sodium chloride, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with dichloromethane:methanol:ammonia (16:1:0.1) as eluents to give 5-(2-diethylamino-ethyl)-3-trifluoromethyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (1 g, 28.4) as a yellow solid.

Workup

  1. additionUpon the completion of the addition
  2. temperaturethe reaction mixture was cooled down to −30˜40° C.
  3. extractionextracted with saturated sodium chloride (100 ml) and dichloromethane (100 ml)
  4. washThe combined organic phase was washed with saturated sodium chloride
  5. dry with materialdried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography with dichloromethane:methanol:ammonia (16:1:0.1) as eluents

Sources & evidence

ORD record
ord-c811eda61a6243c2879faeb8cee3ec56
Source dataset
uspto-grants-2013_01
Patent number
US08362251B2

Reaction notes

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