Dichloromethane → 2-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[3-(1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl]acetamide;hydrochloride

HRID 1050155Notes

Reaction equation

HRID 1050155 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[C:8]([NH:16][C:17](=[O:45])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:26]=[N:27][C:28]([O:34]CC5C=CC(OC)=CC=5)=[C:29]([O:31][CH2:32][CH3:33])[CH:30]=4)=[CH:21][C:20]=3[F:44])[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=2)[CH:3]=[N:2]1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:54]>>[ClH:54].[NH:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[C:8]([NH:16][C:17](=[O:45])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:30]=[C:29]([O:31][CH2:32][CH3:33])[C:28](=[O:34])[NH:27][CH:26]=4)=[CH:21][C:20]=3[F:44])[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=2)[CH:3]=[N:2]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 90423003N-(3-(1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide

Product 1

HCID 904231712-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[3-(1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl]acetamide;hydrochlorideYield 15.9%

Conditions

Temperature
25 °C

Procedure

To a mixture of N-(3-(1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (50 mg, 0.081 mmol) in DCM (10 mL) was added TFA (1 mL, 12.98 mmol). The mixture was stirred at 25° C. for 2 h. The mixture was concentrated and NH4OH (0.5 mL) was added. Then the reaction residue was concentrated and purified by preparative HPLC (Column: ASB C18 150*25 mm; Mobile phase A: Water+0.1% HCl; Mobile phaseB: MeCN; Flowrate: 25 mL/min; Gradient Profile Description: 40-70 (B %)) to yield an off-white solid of N-(3-(1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide hydrochloride (6.95 mg, 0.013 mmol, 15.9% yield): 1H NMR (400 MHz, CD3OD) δ 8.16 (s, 2H), 8.06 (s, 1H), 7.82 (s, 1H), 7.62 (s, 1H), 7.48-7.42 (m, 1H), 7.41-7.34 (m, 3H), 7.33 (s, 1H), 4.15 (q, J=7.2 Hz, 2H), 3.84 (s, 2H), 1.46 (t, J=7.2 Hz, 3H). ES-LCMS m/z 501.2 (M+H). TLC (DCM/MeOH=10:1, Rf=0.2)

Workup

  1. concentrationThe mixture was concentrated
  2. additionNH4OH (0.5 mL) was added
  3. concentrationThen the reaction residue was concentrated
  4. custompurified by preparative HPLC (Column: ASB C18 150*25 mm; Mobile phase A: Water+0.1% HCl; Mobile phaseB: MeCN; Flowrate: 25 mL/min; Gradient Profile Description: 40-70 (B %))

Sources & evidence

ORD record
ord-ac218fd5dc88454e8a712d5777670fa2
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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