Ethyl 3,3,3-trifluoro-2-oxopropanoate → Tert-butyl 4-(3-oxo-2-(trifluoromethyl)-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)naphthalen-1-ylcarbamate

HRID 1035397Notes

Reaction equation

HRID 1035397 reaction equation
[NH2:1][C:2]1[C:7]([NH2:8])=[C:6]([O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=1.[F:28][C:29]([F:38])([F:37])[C:30](=O)[C:31](OCC)=[O:32]>C(O)C>[O:32]=[C:31]1[NH:1][C:2]2[N:3]=[CH:4][CH:5]=[C:6]([O:9][C:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[CH:12][CH:11]=3)[C:7]=2[N:8]=[C:30]1[C:29]([F:38])([F:37])[F:28]

Participants

4

Reactant 2

HCID 2737239Ethyl 3,3,3-trifluoro-2-oxopropanoateHCID 44186229Tert-butyl 4-(2,3-diaminopyridin-4-yloxy)naphthalen-1-ylcarbamate

Product 1

HCID 46900749Tert-butyl 4-(3-oxo-2-(trifluoromethyl)-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)naphthalen-1-ylcarbamate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To tert-butyl 4-(2,3-diaminopyridin-4-yloxy)naphthalen-1-ylcarbamate (1.00 g, 2.73 mmol) dissolved in 20 mL of anhydrous ethanol under argon and at reflux was added the ethyl trifluoropyruvate (697 mg, 0.50 mL, 4.10 mmol). The reaction mixture was stirred at reflux for 3 hours. After cooling at RT, a precipitate was formed, filtered off and rinsed with Et2O. tert-butyl 4-(3-oxo-2-(trifluoromethyl)-3,4-dihydropyrido[2,3-b]pyrazin-8-yloxy)naphthalen-1-ylcarbamate was obtained as a white solid (116 mg, 0.246 mmol, 9%). The filtrate was evaporated under vacuum. The residue was chromatographied (eluent: CH2Cl2/EtOAc: 4/1 towards 0/1) to afford the second isomer as a slightly yellow solid (540 mg, 1.14 mmol, 42%).

Workup

  1. temperatureat reflux
  2. temperatureat reflux for 3 hours
  3. customa precipitate was formed
  4. filtrationfiltered off
  5. washrinsed with Et2O

Sources & evidence

ORD record
ord-9ad7f9914d384bc6a9e8cb71107eb3e5
Source dataset
uspto-grants-2013_10
Patent number
US08546387B2

Reaction notes

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