Trifluoromethanesulfonic anhydride → 2-(4-Fluorophenyl)-3-(methylcarbamoyl)furo[2,3-c]pyridin-5-yl trifluoromethanesulfonate

HRID 44068Notes

Reaction equation

HRID 44068 reaction equation
S([O:8][S:9]([C:12]([F:15])([F:14])[F:13])(=[O:11])=[O:10])(C(F)(F)F)(=O)=O.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[O:32][C:26]3=[CH:27][N:28]=[C:29](O)[CH:30]=[C:25]3[C:24]=2[C:33]([NH:35][CH3:36])=[O:34])=[CH:19][CH:18]=1>N1C=CC=CC=1>[F:15][C:12]([F:13])([F:14])[S:9]([O:8][C:29]1[CH:30]=[C:25]2[C:24]([C:33](=[O:34])[NH:35][CH3:36])=[C:23]([C:20]3[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=3)[O:32][C:26]2=[CH:27][N:28]=1)(=[O:10])=[O:11]

Participants

4

Reactant 2

HCID 67749Trifluoromethanesulfonic anhydrideHCID 178485250HCID 178485250, compound

Product 1

HCID 866399602-(4-Fluorophenyl)-3-(methylcarbamoyl)furo[2,3-c]pyridin-5-yl trifluoromethanesulfonate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Triflic anhydride (Tf2O, 319 μL, 1.89 mmol) was added to a stirring solution of 2-(4-fluorophenyl)-5-hydroxy-N-methylfuro[2,3-c]pyridine-3-carboxamide (270 mg, 0.943 mmol) in pyridine (13 mL) at 0° C. and the mixture was allowed to warm to room temperature. It was allowed to stir for 1 hour then concentrated and diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) to give the expected product 2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-c]pyridin-5-yltrifluoromethanesulfonate (188 mg, 0.449 mmol, 34.8% yield)consistent by LCMS and NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.91 (1 H, s), 8.53-8.61 (1H, m), 8.01-8.11 (2H, m), 7.87 (1H, s), 7.46 (2H, t, J=8.91 Hz), 2.85 (3H, d, J=4.52 Hz). LC-MS retention time: 2.06 min; m/z (MH+): 419. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5u C18 4.6×50 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 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 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. concentrationthen concentrated
  2. additiondiluted with EtOAc
  3. washwashed
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm)

Sources & evidence

ORD record
ord-b40d0863612044a1a457ad58af3e968f
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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