Water → HCID 58779076, compound

HRID 1372700Notes

Reaction equation

HRID 1372700 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11](Cl)=[O:12])=[CH:3]1.[NH2:14][C:15]1[C:16]([Cl:27])=[N:17][C:18]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:19][CH:20]=1.C(N(CC)CC)C.O>C(Cl)Cl>[Cl:27][C:16]1[C:15]([NH:14][C:11]([C:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:2]([CH3:1])[CH:3]=2)=[O:12])=[CH:20][CH:19]=[C:18]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[N:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 151324411-Methyl-1H-indole-3-carbonyl chlorideHCID 72217854HCID 72217854, compound

Product 1

HCID 58779076HCID 58779076, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Oxalyl chloride (1.10 ml, 12.5 mmol) was added to a solution of 1-methylindole-3-carboxylic acid (2.00 g, 11.4 mmol) and DMF (0.18 ml, 2.28 mmol) in methylene chloride (25 ml) and the resulting mixture was stirred for 3 hours at room temperature. The reaction mixture was distilled under reduced pressure to remove the solvent to give 1-methylindole-3-carboxylic acid chloride (2.19 g, 99%) as a pale yellow solid. The resulting 1-methylindole-3-carboxylic acid chloride (752 mg, 3.88 mmol) was added in portions to a solution of ethyl 3-amino-2-chloro-6-pyridylacetate (833 mg, 3.88 mmol) and triethylamine (1.08 ml, 7.77 mmol) in methylene chloride (20 ml) under stirring at 0° C. The reaction mixture was heated under reflux for 8 hours. After cooling to room temperature and addition of water, the mixture was extracted with chloroform. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (2:1, v/v) eluate fractions, ethyl 2-chloro-3-(1-methyl-3-indolylcarbonyl)amino-6-pyridylacetate (859 mg, 60%) was obtained as a yellow solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 8 hours
  3. temperatureAfter cooling to room temperature
  4. extractionthe mixture was extracted with chloroform
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationdistilled under reduced pressure
  8. customto remove the solvent
  9. customThe residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (2:1

Sources & evidence

ORD record
ord-f15fa8bfed83478797b9ce6f6990d6aa
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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