Ethanamine, 2,2,2-trifluoro- → Tert-butyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoate

HRID 1854754Notes

Reaction equation

HRID 1854754 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]=[C:31]([CH:39]=[CH:40][CH:41]=1)[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].[F:42][C:43]([F:47])([F:46])[CH2:44][NH2:45]>>[F:28][C:25]1[CH:24]=[CH:23][C:22]([C:16]2[O:15][C:13]3=[N:14][C:9]([NH:45][CH2:44][C:43]([F:47])([F:46])[F:42])=[C:10]([C:29]4[CH:30]=[C:31]([CH:39]=[CH:40][CH:41]=4)[C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])[CH:11]=[C:12]3[C:17]=2[C:18](=[O:21])[NH:19][CH3:20])=[CH:27][CH:26]=1

Participants

4

Reactant 3

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 2733478Sodium 2-methylbutan-2-olateHCID 90402329Tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate

Product 1

HCID 90402317Tert-butyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoateYield 58%

Conditions

Temperature
80 °C

Procedure

Sodium 2-methylbutan-2-olate (229 mg, 2.08 mmol), tert-butyl 3-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate (200 mg, 0.416 mmol), 2,2,2-trifluoroethanamine (206 mg, 2.08 mmol), Chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (33 mg, 0.042 mmol) was combined, degassed, and taken up in dioxane (8.3 ml) at rt and then was heated to 80° C. LCMS at 30 min showed major peak with M+H matching that of the expected product. The mixture was diluted with EtOAc and washed with 1M HCl aq, and sat NaCl aq. The organic phase was concentrated and triturated with DCM to give the expected product tert-butyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoate (130 mg, 0.239 mmol, 58% yield) consistent by LCMS. LC-MS retention time: 2.13 min; m/z (MH+): 544. 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 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. customdegassed
  2. customtaken up in dioxane (8.3 ml) at rt
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with 1M HCl aq
  5. concentrationwas concentrated
  6. customtriturated with DCM

Sources & evidence

ORD record
ord-bd4c98d801434b75a097d7632919a9fb
Source dataset
uspto-grants-2015_02
Patent number
US08962651B2

Reaction notes

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