Hydrochloric Acid → methyl 2-hydroxy-3-(1H-indole-2-carboxamido)benzoate

HRID 415231Notes

Reaction equation

HRID 415231 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.[NH2:43][C:44]1[C:45]([OH:54])=[C:46]([CH:51]=[CH:52][CH:53]=1)[C:47]([O:49][CH3:50])=[O:48].Cl>CN(C=O)C.O>[OH:54][C:45]1[C:44]([NH:43][C:10]([C:2]2[NH:1][C:9]3[C:4]([CH:3]=2)=[CH:5][CH:6]=[CH:7][CH:8]=3)=[O:12])=[CH:53][CH:52]=[CH:51][C:46]=1[C:47]([O:49][CH3:50])=[O:48]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 72899Indole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12782444Methyl 3-amino-2-hydroxybenzoate

Product 1

HCID 66621063methyl 2-hydroxy-3-(1H-indole-2-carboxamido)benzoateYield 170.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1H-indole-2-carboxylic acid (965 mg, 1.2 mmol) in DMF (15 mL) was added HOBt (740 mg, 1.1 mmol), DIPEA (1.98 g, 3.0 mmol) and EDCI (1.05 g, 1.1 mmol). The mixture was stirred at room temperature for 30 min. Then methyl 3-amino-2-hydroxybenzoate (835 mg, 1 mmol) was added. The mixture was stirred at room temperature for 10 hr. To the resulting mixture, water (10 mL) and aqueous hydrochloric acid (1 N) were added to pH=3, then extracted with ethyl acetate (100 mL×4). The organic phase was washed with saturated sodium bicarbonate solution and brine, dried by anhydrous sodium sulfate and concentrated to yield the crude product. The crude product was purified by column chromatography (silica gel, petroleum ether:ethyl acetate 20:1) to obtain methyl 2-hydroxy-3-(1H-indole-2-carboxamido)benzoate as a solid (530 mg, yield 26%). LC-MS (ESI) m/z 296 [M+1]−.

Workup

  1. stirringThe mixture was stirred at room temperature for 10 hr
  2. extractionextracted with ethyl acetate (100 mL×4)
  3. washThe organic phase was washed with saturated sodium bicarbonate solution and brine
  4. dry with materialdried by anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto yield the crude product
  7. customThe crude product was purified by column chromatography (silica gel, petroleum ether:ethyl acetate 20:1)

Sources & evidence

ORD record
ord-67b30fb1adcb47919d7bd0e3934399ef
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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