Triethylamine → (E)-3-(4-{(S)-1-[2-(2-methyl-1H-indol-3-yl)-acetyl]-pyrrolidin-2-yl}-phenyl)-acrylic acid methyl ester

HRID 1802761Notes

Reaction equation

HRID 1802761 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:18])/[CH:5]=[CH:6]/[C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]2[CH2:17][CH2:16][CH2:15][NH:14]2)=[CH:9][CH:8]=1.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[CH3:48][C:49]1[NH:50][C:51]2[C:56]([C:57]=1[CH2:58][C:59](O)=[O:60])=[CH:55][CH:54]=[CH:53][CH:52]=2>CN(C)C=O.ClCCl>[CH3:2][O:3][C:4](=[O:18])/[CH:5]=[CH:6]/[C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[C:59](=[O:60])[CH2:58][C:57]2[C:56]3[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=3)[NH:50][C:49]=2[CH3:48])=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 5891072-Methyl-1H-indole-3-acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67158659(E)-3-((S)-4-pyrrolidin-2-yl-phenyl)-acrylic acid methyl ester hydrochloride

Product 1

HCID 67158759(E)-3-(4-{(S)-1-[2-(2-methyl-1H-indol-3-yl)-acetyl]-pyrrolidin-2-yl}-phenyl)-acrylic acid methyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (E)-3-((S)-4-pyrrolidin-2-yl-phenyl)-acrylic acid methyl ester hydrochloride (0.3 g, 1.12 mmol) in N,N-dimethylformamide (20 mL) was added sequentially triethylamine (0.5 mL, 3.58 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.24 g, 1.25 mmol), 1-hydroxybenzotriazole (0.17 g, 1.25 mmol) and 2-methylindole-3-acetic acid (0.235 g, 1.24 mmol). The reaction was stirred for 16 h and diluted with dichloromethane, and the solution was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (2% methanol in dichloromethane) to obtain (E)-3-(4-{(S)-1-[2-(2-methyl-1H-indol-3-yl)-acetyl]-pyrrolidin-2-yl}-phenyl)-acrylic acid methyl ester as a colorless oil (0.42 g, 1.03 mmol, 93% yield).

Workup

  1. washthe solution was washed with a saturated aqueous solution of sodium chloride
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by silica gel column chromatography (2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a8076f69a55742b5aa81ac0dc76d7c6b
Source dataset
uspto-grants-2013_01
Patent number
US08349883B2

Reaction notes

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