Trifluoroacetic acid → 7-(1-Ethyl-1H-pyrazol-4-yl)-5-({[(3S)-3-fluoro-3-piperidinyl]methyl}oxy)-1,6-naphthyridine

HRID 473328Notes

Reaction equation

HRID 473328 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[C:10]([O:18][CH2:19][C@:20]3([F:33])[CH2:25][CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]3)[N:9]=2)[CH:5]=[N:4]1)[CH3:2].FC(F)(F)C(O)=O>C(Cl)Cl.CO>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[C:10]([O:18][CH2:19][C@:20]3([F:33])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21]3)[N:9]=2)[CH:5]=[N:4]1)[CH3:2]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 682098821,1-Dimethylethyl (3S)-3-({[7-(1-ethyl-1H-pyrazol-4-yl)-1,6-naphthyridin-5-yl]oxy}methyl)-3-fluoro-1-piperidinecarboxylate

Product 1

HCID 545755127-(1-Ethyl-1H-pyrazol-4-yl)-5-({[(3S)-3-fluoro-3-piperidinyl]methyl}oxy)-1,6-naphthyridineYield 72.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,1-dimethylethyl (3S)-3-({[7-(1-ethyl-1H-pyrazol-4-yl)-1,6-naphthyridin-5-yl]oxy}methyl)-3-fluoro-1-piperidinecarboxylate (1.1 g, 2.415 mmol) in DCM (3 ml) was added trifluoroacetic acid (3 ml, 38.9 mmol) and this was stirred at room temp for 3 h. The reaction had gone to completion and so was concentrated in vacuo to yield the crude product. The TFA salt was dissolved in methanol and loaded onto an SCX cartridge (20 g). The impurities were eluted with methanol, and the product was eluted with 2M ammonia in methanol. The filtrate was concentrated in vacuo to yield a cream gummy solid (620 mg). This was purified by large-scale MDAP (Method C). The appropriate vials were combined and concentrated in vacuo to give the product as the TFA salt. To form the free base, this was dissolved in methanol and purified through an SCX cartridge (20 g) eluting with methanol. The product was eluted with 2M ammonia in methanol. The filtrate was concentrated in vacuo to yield the title compound as a clear glass (500 mg).

Workup

  1. concentrationso was concentrated in vacuo
  2. customto yield the crude product
  3. washThe impurities were eluted with methanol
  4. washthe product was eluted with 2M ammonia in methanol
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-6ca3f26967aa43688a9d29f5621201b5
Source dataset
uspto-grants-2014_01
Patent number
US08633319B2

Reaction notes

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