Dichloromethane → N-(6-ethoxy-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide, hydrochloride

HRID 576173Notes

Reaction equation

HRID 576173 reaction equation
[CH2:1]([O:3][C:4]1[N: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])[CH3:2].C(O)(C(F)(F)F)=O.[OH-].[Na+].C(Cl)[Cl:54]>>[ClH:54].[CH2:1]([O:3][C:4]1[N: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:43])[F:42])[CH3:2]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 90416521N-(6-ethoxy-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-((4-me thoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide

Product 1

HCID 90422510N-(6-ethoxy-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide, hydrochlorideYield 49.8%

Conditions

Temperature
25 °C

Procedure

To a mixture of N-(6-ethoxy-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (40 mg, 0.067 mmol) in DCM (10 mL) was added TFA (0.701 mL, 9.10 mmol). The mixture was stirred at 25° C. for 2 h. Then the reaction residue was added to NaOH (2.5 m, 3 mL) and concentrated. The crude material was purified by preparative HPLC (MeCN/H2O as eluants, basic condition) to yield a white solid of N-(6-ethoxy-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide, hydrochloride (15.66 mg, 0.030 mmol, 49.8% yield): 1H NMR (400 MHz, CD3OD) δ 8.50 (s, 1H), 8.29 (d, J=2.0 Hz, 1H), 7.49-7.41 (m, 1H), 7.40-7.31 (m, 3H), 7.26 (d, J=2.0 Hz, 1H), 4.47 (m, 2H), 4.15 (m, 2H), 3.82 (s, 2H), 1.49 (t, J=7.0 Hz, 3H), 1.40 (t, J=7.0 Hz, 3H); ES-LCMS m/z 480.2 (M+H).

Workup

  1. concentrationconcentrated
  2. customThe crude material was purified by preparative HPLC (MeCN/H2O as eluants, basic condition)

Sources & evidence

ORD record
ord-bb648f73300e48e6acf64a4ebfcd4c1b
Source dataset
uspto-grants-2015_05
Patent number
US09035063B2

Reaction notes

Loading…