Trifluoroacetic acid → HCID 78427305, compound

HRID 1050184Notes

Reaction equation

HRID 1050184 reaction equation
[F:1][C:2]([F:46])([CH2:44][OH:45])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:39])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:20]=[N:21][C:22]([O:28]CC4C=CC(OC)=CC=4)=[C:23]([O:25][CH2:26][CH3:27])[CH:24]=3)=[CH:15][C:14]=2[F:38])=[CH:6][C:5]=1[C:40]([F:43])([F:42])[F:41].C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:46][C:2]([F:1])([CH2:44][OH:45])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:39])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[C:23]([O:25][CH2:26][CH3:27])[C:22](=[O:28])[NH:21][CH:20]=3)=[CH:15][C:14]=2[F:38])=[CH:6][C:5]=1[C:40]([F:41])([F:42])[F:43]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90423309HCID 90423309, compound

Product 1

HCID 78427305HCID 78427305, compoundYield 41.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of N-(4-(2,2-difluoro-3-hydroxypropyl)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (50 mg, 0.077 mmol) in DCM (5 mL) was added TFA (0.012 mL, 0.154 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: 26-56 (B %)) to give N-(4-(2,2-difluoro-3-hydroxypropyl)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide (16.72 mg, 0.032 mmol, 41.0% yield): 1H NMR (400 MHz, CD3OD-d4) δ 8.01 (s, 1H), 7.76 (d, J=8.4 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.40 (d, J=7.5 Hz, 1H), 7.36-7.26 (m, 3H), 7.23 (s, 1H), 4.12 (d, J=7.1 Hz, 2H), 3.80 (s, 2H), 3.68 (t, J=12.8 Hz, 2H), 3.41 (t, J=17.1 Hz, 2H), 1.45 (t, J=6.9 Hz, 3H). ES-LCMS m/z 529 (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: 26-56 (B %))

Sources & evidence

ORD record
ord-6d1f9bfba919460b9fb60fc2210f18df
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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