3-Amino-2-(4-chloro-phenylethynyl)-benzoic acid methyl ester → 2-(4-Chloro-phenyl)-1H-indole-4-carboxylic acid methyl ester

HRID 2298939

Reaction equation

HRID 2298939 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH2:10])[C:5]=1[C:11]#[C:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1>C(#N)C.[Pd](Cl)Cl>[CH3:1][O:2][C:3]([C:4]1[C:5]2[CH:11]=[C:12]([C:13]3[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=3)[NH:10][C:6]=2[CH:7]=[CH:8][CH:9]=1)=[O:20]

Participants

4

Reactant 1

HCID 183400043-Amino-2-(4-chloro-phenylethynyl)-benzoic acid methyl ester

Product 1

HCID 183400022-(4-Chloro-phenyl)-1H-indole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

3-amino-2-(4-chloro-phenylethynyl)-benzoic acid methyl ester (0.73 g, 2.54 mmol) and palladium (II) chloride (23 mg, 0.13 mmol) were combined in 10 mL acetonitrile. The yellow solution was stirreed under argon at 75° C. for 17 h. The solvent was removed in vacuo leaving an orange solid which was purified by flash chromatography eluting with 50 to 100% CH-Cl3/hecanes. 2-(4-chloro-henyl)-1H-indole-4-carboxylic acid methyl ester; 0.53 g (72%) was isolated as an off-white solid: m.p. 150.0-151.5° C.; 1H NMR (300 MHz, d6-DMSO) 3.93 (s, 3H), 7.23 (app t, J=7.8 Hz, 1H), 7.41 (d, J=1.8 Hz, 1H), 7.57 (d, J=8.7 Hz, 2H), 7.68 (d, J=7.8 Hz, 1H), 7.75 (dd, J=7.5, 0.9 Hz, 1H), 7.95 (d, J=8.7 Hz, 2H), 11.99 (br s, 1H). HRMS (MALDI, MH+) Calcd for C16H12ClNO2: 286.0635. Found: 286.0631.

Workup

  1. customThe solvent was removed in vacuo
  2. customleaving an orange solid which
  3. customwas purified by flash chromatography
  4. washeluting with 50 to 100% CH-Cl3/hecanes
  5. custom0.53 g (72%) was isolated as an off-white solid

Sources & evidence

ORD record
ord-7258ffc4484e4acb8496f923ce192f88
Source dataset
uspto-grants-2002_12
Patent number
US06495541B1

Linked notes

Loading…