Triethylamine → (R)-N-(3-(1-(6-chloropyrazin-2-yloxy)ethyl)phenyl)-3-(trifluoromethyl)benzamide

HRID 572226Notes

Reaction equation

HRID 572226 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([O:8][C@@H:9]([C:11]2[CH:12]=[C:13]([CH:15]=[CH:16][CH:17]=2)[NH2:14])[CH3:10])[CH:5]=[N:4][CH:3]=1.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=1)[C:23](O)=[O:24].Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.ClCCl>[Cl:1][C:2]1[N:7]=[C:6]([O:8][C@@H:9]([C:11]2[CH:12]=[C:13]([NH:14][C:23](=[O:24])[C:22]3[CH:26]=[CH:27][CH:28]=[C:20]([C:19]([F:18])([F:29])[F:30])[CH:21]=3)[CH:15]=[CH:16][CH:17]=2)[CH3:10])[CH:5]=[N:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 99633-(Trifluoromethyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86641863(R)-3-(1-(6-chloropyrazin-2-yloxy)ethyl)aniline

Product 1

HCID 86641864(R)-N-(3-(1-(6-chloropyrazin-2-yloxy)ethyl)phenyl)-3-(trifluoromethyl)benzamideYield 40.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of (R)-3-(1-(6-chloropyrazin-2-yloxy)ethyl)aniline (160 mg, 0.64 mmol), 3-trifluoromethylbenzoic acid (183 mg, 0.96 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (246 mg, 1.28 mmol), 4-dimethylamino pyridine (4 mg, 0.032 mmol) and triethylamine (0.36 mL, 2.57 mmol) in dichloromethane (6 mL) was stirred at room temperature for 18 hours. After this time the mixture was diluted with dichloromethane (30 mL), washed successively with saturated aqueous sodium hydrogen carbonate (2×20 mL) and brine (20 mL), dried (Na2SO4) and concentrated under reduced pressure to give an orange oil which was purified by flash chromatography (silica, ethyl acetate/hexanes) to give (R)—N-(3-(1-(6-chloropyrazin-2-yloxy)ethyl)phenyl)-3-(trifluoromethyl)benzamide (110 mg, 30% over 2 steps) as a yellow foam.

Workup

  1. washwashed successively with saturated aqueous sodium hydrogen carbonate (2×20 mL) and brine (20 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customto give an orange oil which
  5. customwas purified by flash chromatography (silica, ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-29c4bf24cf1e429a9bb32df43d5b05fa
Source dataset
uspto-grants-2015_05
Patent number
US09029386B2

Reaction notes

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