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

HRID 1050175Notes

Reaction equation

HRID 1050175 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[N:34]([CH3:35])[N:33]=[C:32]([C:36]([CH3:42])([CH3:41])[C:37]([F:40])([F:39])[F:38])[CH:31]=3)=[O:28])=[C:22]([F:43])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10]CC1C=CC(OC)=CC=1)[CH3:2].C(Cl)[Cl:45]>C(O)(C(F)(F)F)=O>[ClH:45].[CH2:1]([O:3][C:4]1[C:9](=[O:10])[NH:8][CH:7]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]3[N:34]([CH3:35])[N:33]=[C:32]([C:36]([CH3:42])([CH3:41])[C:37]([F:39])([F:40])[F:38])[CH:31]=3)=[O:28])=[C:22]([F:43])[CH:21]=2)[CH:5]=1)[CH3:2]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 904227162-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(1-methyl-3-(1, 1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-yl)acetamide

Product 1

HCID 904232232-[4-(5-ethoxy-6-oxo-1H-pyridin-3-yl)-2-fluorophenyl]-N-[2-methyl-5-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrazol-3-yl]acetamide;hydrochlorideYield 63.9%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A mixture of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(1-methyl-3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-yl)acetamide (150 mg, 0.250 mmol) in TFA.DCM (solvate) (10 mL, 10%) was stirred for 0.5 h at 25° C. Then the mixture was concentrated to give the residue which purified by preparative HPLC (column: ASB C18 150*25 mm/Mobile phase A: Water (Water+0.1% HCl)/Mobile phaseB: Acetonitrile/Gradient: 37-67(B %)/Flowrate: 25 mL/min/Run time: 15 min) to yield 2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(1-methyl-3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-yl)acetamide hydrochloride (83.1 mg, 0.160 mmol, 63.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.48-7.41 (m, 1H), 7.39 (s, 1H), 7.37 (d, J=3.5 Hz, 1H), 7.33 (d, J=2.0 Hz, 1H), 7.26 (d, J=2.0 Hz, 1H), 6.29 (s, 1H), 4.15 (q, J=7.0 Hz, 2H), 3.86 (s, 2H), 3.73 (s, 3H), 1.51 (s, 6H), 1.50-1.45 (m, 3H). ES-LCMS m/z 481 (M+H).

Workup

  1. concentrationThen the mixture was concentrated
  2. customto give the residue which
  3. custompurified by preparative HPLC (column: ASB C18 150*25 mm/Mobile phase A: Water (Water+0.1% HCl)/Mobile phaseB: Acetonitrile/Gradient: 37-67(B %)/Flowrate: 25 mL/min/Run time: 15 min)

Sources & evidence

ORD record
ord-f8086a54a1b74d53a5b42b9c7aa8f87f
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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