(S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid chloride → (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indol-6-yl}-amide

HRID 386667Notes

Reaction equation

HRID 386667 reaction equation
[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([CH3:19])=[C:15]([NH2:18])[CH:16]=2)[CH:11]=[CH:10]1)([CH3:4])([CH3:3])[CH3:2].[F:22][C:23]1[CH:28]=[CH:27][C:26]([C@@H:29]2[CH2:34][C:33](=[O:35])[NH:32][CH:31]=[C:30]2[C:36](Cl)=[O:37])=[CH:25][CH:24]=1>ClCCl.C(N(CC)CC)C.CN(C1C=CN=CC=1)C>[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([CH3:19])=[C:15]([NH:18][C:36]([C:30]3[C@H:29]([C:26]4[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=4)[CH2:34][C:33](=[O:35])[NH:32][CH:31]=3)=[O:37])[CH:16]=2)[CH:11]=[CH:10]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 59377403(S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid chlorideHCID 59377421HCID 59377421, compound

Product 1

HCID 59377436(S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indol-6-yl}-amide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indol-6-ylamine was dissolved in 10 ml dichloromethane and 0.25 ml triethylamine. The solution was cooled to 0° C. and 150 mg of (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid chloride in 1.5 ml dichloromethane was added. The resulting mixture was stirred at 0° C. for one hour, then at room temperature for two hours. DMAP (100 mg) was added and the mixture stirred for another hour. The reaction mixture was then partitioned between pH 7 phosphate buffer and ethyl acetate. The organic layer was dried over sodium sulfate, filtered, concentrated under reduced pressure, and the residue purified by flash chromatography to give 70 mg of (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indol-6-yl}-amide e/z 522 (M+H).

Workup

  1. waitat room temperature for two hours
  2. stirringthe mixture stirred for another hour
  3. customThe reaction mixture was then partitioned between pH 7 phosphate buffer and ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-425750dc45694d32ad627cc7183327de
Source dataset
uspto-grants-2013_02
Patent number
US08372865B2

Reaction notes

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