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

HRID 1854755Notes

Reaction equation

HRID 1854755 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:42][C:18]3=[N:19][C:20]([NH:36][CH2:37][C:38]([F:41])([F:40])[F:39])=[C:21]([C:23]4[CH:24]=[C:25]([CH:33]=[CH:34][CH:35]=4)[C:26]([O:28]C(C)(C)C)=[O:27])[CH:22]=[C:17]3[C:16]=2[C:43](=[O:46])[NH:44][CH3:45])=[CH:11][CH:10]=1>C(Cl)Cl>[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:42][C:18]3=[N:19][C:20]([NH:36][CH2:37][C:38]([F:39])([F:41])[F:40])=[C:21]([C:23]4[CH:24]=[C:25]([CH:33]=[CH:34][CH:35]=4)[C:26]([OH:28])=[O:27])[CH:22]=[C:17]3[C:16]=2[C:43](=[O:46])[NH:44][CH3:45])=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90402317Tert-butyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoate

Product 1

HCID 904025453-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoic acidYield 83.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (921 μl, 11.9 mmol) was added to a stirring solution of 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) in DCM (2.4 ml) at rt. The reaction was allowed to stir for 2 h then concentrated azeotroping with toluene to dryness. The resulting solid was triturated with DCM to give the expected product 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoic acid (97 mg, 0.20 mmol, 83% yield) consistent by LCMS and NMR. LC-MS retention time: 1.73 min; m/z (MH+): 488. 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. 1H NMR (400 MHz, DMSO-d6) δ 13.07 (br. s, 1H), 8.37-8.30 (m, J=4.5 Hz, 1H), 8.05-7.94 (m, 4H), 7.70-7.66 (m, 3H), 7.34 (t, J=8.9 Hz, 2H), 6.67 (s, 1H), 4.23-4.10 (m, J=3.0 Hz, 2H), 2.80 (d, J=4.8 Hz, 3H).

Workup

  1. concentrationthen concentrated
  2. customazeotroping with toluene to dryness
  3. customThe resulting solid was triturated with DCM

Sources & evidence

ORD record
ord-df110a05573940e583dc832c77456385
Source dataset
uspto-grants-2015_02
Patent number
US08962651B2

Reaction notes

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