Hydroxyphenylacetic acid → HCID 10450054, compound

HRID 1272444Notes

Reaction equation

HRID 1272444 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2.[OH:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25](O)=[O:26])=[CH:20][CH:19]=1.Cl.CN(CCCN=C=NCC)C>C(#N)C>[OH:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)=[O:26])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 127Hydroxyphenylacetic acidHCID 7359662-(2-Aminophenyl)indoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 10450054HCID 10450054, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
23 °C

Procedure

1 g (4.8 mmol) 2-(2-Aminophenyl) indole was dissolved in 200 ml acetonitrile. 1.46 g (9.6 mmol, 2 eq) of 4-hydroxyphenylacetic acid were dissolved in 50 ml acetonitrile and added to the solution. To the mixture were added 1.84 g (9.6 mmol, 2 eq) of EDC (dimethylaminopropyl ethylcarbodiimide hydrochloride). The reaction mixture was stirred at 23° C. for 16 hours. The solvent was removed and the residue was dissolved in 100 ml ethylacetate:methanol (10:1). It was extracted twice with 100 ml of aqueous 1M HCl as well as 100 ml of aqueous, saturated sodium bicarbonate solution. The aqueous phases were re-extracted with EtOAc, respectively. The combined organic phases were dried over magnesium sulfate. The crude product was chromatographed on silica using a ethylacetate/hexane gradient (10%–50%) to obtain 1.23 g of the amide as a pink colored powder in an overall yield of 75%. 100% Purity by LC/MS (230 DAD) Mass-spec [M+H+]=343.9 1H NMR (MeOH-d4): 3.60 s (2H), 6.10 s (1H), 6.70 d, 8 Hz (2H), 7.03 t, 8 Hz (1H), 7.09–7.13 m (3H), 7.25 t, 7 Hz (1H), 7.34 m (2H), 7.49 d, 8 Hz (1H), 7.53 d, 8 Hz (1H), 7.95 d, 8 Hz (1H).

Workup

  1. additionadded to the solution
  2. customThe solvent was removed
  3. dissolutionthe residue was dissolved in 100 ml ethylacetate:methanol (10:1)
  4. extractionIt was extracted twice with 100 ml of aqueous 1M HCl as well as 100 ml of aqueous, saturated sodium bicarbonate solution
  5. extractionThe aqueous phases were re-extracted with EtOAc
  6. dry with materialThe combined organic phases were dried over magnesium sulfate
  7. customThe crude product was chromatographed on silica using a ethylacetate/hexane gradient (10%–50%)

Sources & evidence

ORD record
ord-ac3f6837d1f94faea13e952a56ed18f9
Source dataset
uspto-grants-2007_04
Patent number
US07208493B2

Reaction notes

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