Triethylamine → methyl 2,4-dichloro-6-(5-fluoro-6-((R)-1-(1-(2,2,2-trifluoroacetamido)cyclopropanecarboxamido)ethyl)pyridin-3-yl)benzoate

HRID 1374173Notes

Reaction equation

HRID 1374173 reaction equation
[Cl-].[Cl:2][C:3]1[C:4]([C:20]([O:22][CH3:23])=[O:21])=[C:5]([C:10]2[CH:11]=[C:12]([F:19])[C:13]([C@H:16]([NH3+:18])[CH3:17])=[N:14][CH:15]=2)[CH:6]=[C:7]([Cl:9])[CH:8]=1.[F:24][C:25]([F:36])([F:35])[C:26]([NH:28][C:29]1([C:32](O)=[O:33])[CH2:31][CH2:30]1)=[O:27].Cl.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl>[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[CH:6]=[C:5]([C:10]2[CH:15]=[N:14][C:13]([C@H:16]([NH:18][C:32]([C:29]3([NH:28][C:26](=[O:27])[C:25]([F:24])([F:35])[F:36])[CH2:30][CH2:31]3)=[O:33])[CH3:17])=[C:12]([F:19])[CH:11]=2)[C:4]=1[C:20]([O:22][CH3:23])=[O:21]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 129888001-(2,2,2-Trifluoroacetamido)cyclopropane-1-carboxylic acidHCID 86602347(1R)-1-{5-[3,5-dichloro-2-(methoxycarbonyl)phenyl]-3-fluoro-pyridin-2-yl}ethanaminium chloride

Product 1

HCID 44432220methyl 2,4-dichloro-6-(5-fluoro-6-((R)-1-(1-(2,2,2-trifluoroacetamido)cyclopropanecarboxamido)ethyl)pyridin-3-yl)benzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (1R)-1-{5-[3,5-dichloro-2-(methoxycarbonyl)phenyl]-3-fluoro-pyridin-2-yl}ethanaminium chloride (0.277 g, 0.73 mmol), 1-[(trifluoroacetyl)amino]cyclo-propanecarboxylic acid (0.160 g, 0.812 mmol), 1-ethyl-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.311 g, 1.62 mmol), 1-hydroxy-7-azabenzotriazole (0.010 g, 0.15 mmol), and triethylamine (0.45 mL, 3.25 mmol) in 5 mL CH2Cl2 was stirred at room temperature for 3 days. The solution was washed with aqueous sodium bicarbonate and brine, dried over Na2SO4, filtered and concentrated. The residue was subjected to silica gel chromatography eluted with 10–30% ethyl acetate in hexanes to provide methyl 2,4dichloro-6-(5-fluoro-6-{(1R)-1-[({1-[(trifluoroacetyl)amino]cyclopropyl}carbonyl)amino]ethyl}pyridin-3-yl)benzoate that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 522.05 for M+H+.

Workup

  1. washThe solution was washed with aqueous sodium bicarbonate and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. washeluted with 10–30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-912129db65a648ddbe96ca69d5b6993e
Source dataset
uspto-grants-2007_01
Patent number
US07163951B2

Reaction notes

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