Ethanamine, 2,2,2-trifluoro- → 5-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)-2-methoxybenzoic acid

HRID 1854756Notes

Reaction equation

HRID 1854756 reaction equation
CC([O-])(CC)C.[Na+].Cl[C:9]1[N:14]=[C:13]2[O:15][C:16]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[C:17]([C:18](=[O:21])[NH:19][CH3:20])[C:12]2=[CH:11][C:10]=1[C:29]1[CH:30]=[CH:31][C:32]([O:38][CH3:39])=[C:33]([CH:37]=1)[C:34]([OH:36])=[O:35].[F:40][C:41]([F:45])([F:44])[CH2:42][NH2:43]>>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:16]2[O:15][C:13]3=[N:14][C:9]([NH:43][CH2:42][C:41]([F:45])([F:44])[F:40])=[C:10]([C:29]4[CH:30]=[CH:31][C:32]([O:38][CH3:39])=[C:33]([CH:37]=4)[C:34]([OH:36])=[O:35])[CH:11]=[C:12]3[C:17]=2[C:18](=[O:21])[NH:19][CH3:20])=[CH:23][CH:24]=1

Participants

4

Reactant 3

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 2733478Sodium 2-methylbutan-2-olateHCID 904023855-(6-Chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)-2-methoxybenzoic acid

Product 1

HCID 904023155-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)-2-methoxybenzoic acidYield 13.1%

Conditions

Temperature
90 °C

Procedure

Sodium 2-methylbutan-2-olate (333 mg, 3.02 mmol), 5-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)-2-methoxybenzoic acid (275 mg, 0.605 mmol), 2,2,2-trifluoroethanamine (299 mg, 3.02 mmol), Chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (48 mg, 0.060 mmol) were combined, degassed, and taken up in dioxane (12 ml) at rt and then was heated to 90° C. The reaction was allowed to stir for 1 h. The mixture was then diluted with EtOAc and washed with 1M HCl aq, and sat NaCl aq. The organic phase was concentrated the resulting residue was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give the expected product 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)-2-methoxybenzoic acid (41 mg, 0.079 mmol, 13% yield) consistent by LCMS. LC-MS retention time: 1.87 min; m/z (MH+): 518. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% MeOH/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% MeOH/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. customdegassed
  2. customtaken up in dioxane (12 ml) at rt
  3. additionThe mixture was then diluted with EtOAc
  4. washwashed with 1M HCl aq
  5. concentrationwas concentrated the resulting residue
  6. customwas purified by preparative reverse phase HPLC on a C18 column
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ca48d199591e4406bb1aedc9dbc9458a
Source dataset
uspto-grants-2015_02
Patent number
US08962651B2

Reaction notes

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