Trifluoroacetic acid → 2-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[3-(2H-tetrazol-5-yl)-5-(trifluoromethyl)phenyl]acetamide

HRID 1050191Notes

Reaction equation

HRID 1050191 reaction equation
[N:1]1[NH:2][N:3]=[N:4][C:5]=1[C:6]1[CH:7]=[C:8]([NH:16][C:17](=[O:45])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:26]=[N:27][C:28]([O:34]CC4C=CC(OC)=CC=4)=[C:29]([O:31][CH2:32][CH3:33])[CH:30]=3)=[CH:21][C:20]=2[F:44])[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:4]1[NH:3][N:2]=[N:1][C:5]=1[C:6]1[CH:7]=[C:8]([NH:16][C:17](=[O:45])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[C:29]([O:31][CH2:32][CH3:33])[C:28](=[O:34])[NH:27][CH:26]=3)=[CH:21][C:20]=2[F:44])[CH:9]=[C:10]([C:12]([F:14])([F:13])[F:15])[CH:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90422813N-(3-(2H-tetrazol-5-yl)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl) oxy)pyridin-3-yl)-2-fluorophenyl)acetamide

Product 1

HCID 784274302-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[3-(2H-tetrazol-5-yl)-5-(trifluoromethyl)phenyl]acetamideYield 20.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a mixture of N-(3-(2H-tetrazol-5-yl)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (30 mg, 0.048 mmol) in DCM (5 mL) was added TFA (7.42 μL, 0.096 mmol). The mixture was stirred at 20° C. for 1 h. LCMS showed the reaction was finished. The mixture was concentrated to give crude product, which was purified by preparative HPLC (Column: ASB C18 150*25 mm; Mobile phase A: Water+0.1% HCl; Mobile phaseB: MeCN; Flowrate: 25 mLl/min; Gradient Profile Description: 30-66 (B %)) to give N-(3-(2H-tetrazol-5-yl)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide (5.12 mg, 10.01 μmol, 20.8% yield): 1H NMR (400 MHz, DMSO-d6) δ 11.83 (br. s., 1H), 11.33 (s, 1H), 10.85 (s, 1H), 8.69-8.57 (m, 1H), 8.21 (s, 1H), 8.01 (s, 1H), 7.47 (d, J=11.7 Hz, 1H), 7.42-7.27 (m, 3H), 7.12 (br. s., 1H), 4.03 (d, J=6.8 Hz, 2H), 3.79 (s, 2H), 1.31 (t, J=6.8 Hz, 3H). ES-LCMS m/z 503 (M+H).

Workup

  1. concentrationThe mixture was concentrated
  2. customto give crude product, which
  3. customwas purified by preparative HPLC (Column: ASB C18 150*25 mm; Mobile phase A: Water+0.1% HCl; Mobile phaseB: MeCN; Flowrate: 25 mLl/min; Gradient Profile Description: 30-66 (B %))

Sources & evidence

ORD record
ord-0c09a346080f4c468ea5ef17858b6991
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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