Triethylamine → methyl 4-chloro-5-(1-methyl-1H-indol-5-yl)-2-({[3-(methyloxy)phenyl]acetyl}amino)benzoate

HRID 2174550Notes

Reaction equation

HRID 2174550 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]([Cl:12])[C:9]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([CH3:22])[CH:17]=[CH:16]3)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(N(CC)CC)C.[CH3:30][O:31][C:32]1[CH:33]=[C:34]([CH2:38][C:39](Cl)=[O:40])[CH:35]=[CH:36][CH:37]=1>ClCCl>[Cl:12][C:10]1[C:9]([C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([CH3:22])[CH:17]=[CH:16]3)=[CH:8][C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([NH:1][C:39](=[O:40])[CH2:38][C:34]2[CH:35]=[CH:36][CH:37]=[C:32]([O:31][CH3:30])[CH:33]=2)[CH:11]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27332463-Methoxyphenylacetyl chlorideHCID 68291444methyl 2-amino-4-chloro-5-(1-methyl-1H-indol-5-yl)benzoate2×

Product 1

HCID 68291071methyl 4-chloro-5-(1-methyl-1H-indol-5-yl)-2-({[3-(methyloxy)phenyl]acetyl}amino)benzoateYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of methyl 2-amino-4-chloro-5-(1-methyl-1H-indol-5-yl)benzoate (Intermediate 45) (150 mg, 0.427 mmol) in dichloromethane (20 mL) at 0° C. was added triethylamine (0.131 mL, 0.940 mmol) and [3-(methyloxy)phenyl]acetyl chloride (Acros Organics, 79 mg, 0.427 mmol) was added dropwise. The reaction mixture was stirred from 0° C. to RT for 1 h before being quenched with 1N HCl. The organic layer was separated and washed successively with sat. NaHCO3 and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The product was purified by chromatography using a cyclohexane to cyclohexane/EtOAc 80:20 as eluant. The appropriate fractions were combined and concentrated in vacuo to give the title compound methyl 4-chloro-5-(1-methyl-1H-indol-5-yl)-2-({[3-(methyloxy)phenyl]acetyl}amino)benzoate (150 mg, 0.324 mmol, 76% yield) as a white amorphous solid. LCMS: (M+H)+=463; Rt=4.23 min.

Workup

  1. additionwas added dropwise
  2. custombefore being quenched with 1N HCl
  3. customThe organic layer was separated
  4. washwashed successively with sat. NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by chromatography
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a3e00d78c3484ad6816535d314453b24
Source dataset
uspto-grants-2015_06
Patent number
US09061998B2

Reaction notes

Loading…