Dichloromethane → 2-[4-(4-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[6-(1-hydroxy-2-methylpropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl]acetamide

HRID 1050131Notes

Reaction equation

HRID 1050131 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([O:10]CC2C=CC(OC)=CC=2)[N:7]=[CH:6][C:5]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]2[CH:31]=[N:32][C:33]([C:40]([CH3:44])([CH3:43])[CH2:41][OH:42])=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=2)=[O:28])=[C:22]([F:45])[CH:21]=1)[CH3:2].C(Cl)Cl>C(O)(C(F)(F)F)=O>[CH2:1]([O:3][C:4]1[C:5]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[CH:31]=[N:32][C:33]([C:40]([CH3:44])([CH3:43])[CH2:41][OH:42])=[C:34]([C:36]([F:39])([F:37])[F:38])[CH:35]=3)=[O:28])=[C:22]([F:45])[CH:21]=2)=[CH:6][NH:7][C:8](=[O:10])[CH:9]=1)[CH3:2]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 904229742-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(6-(1-hydroxy-2-methylpropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)acetamide

Product 1

HCID 784270252-[4-(4-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[6-(1-hydroxy-2-methylpropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl]acetamideYield 54%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(6-(1-hydroxy-2-methylpropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)acetamide (20 mg, 0.032 mmol) in TFA in DCM (5 mL, 3.72 mmol) was stirred at 25° C. After LCMS analysis showed the starting material was consumed, the solvent was removed in vacuo to give the crude product, which was purified by preparative HPLC (under neutral condition) to yield a white solid of 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(6-(1-hydroxy-2-methylpropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)acetamide (8.8 mg, 0.017 mmol, 54% yield): 1H NMR (400 MHz, CD3OD) δ 8.91 (s, 1H), 8.46 (d, J=2.0 Hz, 1H), 7.40-7.35 (m, 2H), 7.24-7.21 (m, 2H), 5.98 (s, 1H), 4.13-4.08 (m, 2H), 3.82 (s, 4H), 1.37 (t, J=7.0 Hz, 9H); ES-LCMS m/z: 508.2 (M+H).

Workup

  1. customwas consumed
  2. customthe solvent was removed in vacuo
  3. customto give the crude product, which
  4. customwas purified by preparative HPLC (under neutral condition)

Sources & evidence

ORD record
ord-0f32f02be2f1430c8c78a49f17aa7a93
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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