Trifluoroacetic acid → N-{[(3S)-3-Fluoro-3-piperidinyl]methyl}-7-{1-[(methyloxy)methyl]-1H-pyrazol-4-yl}-1,6-naphthyridin-5-amine

HRID 473327Notes

Reaction equation

HRID 473327 reaction equation
[F:1][C@@:2]1([CH2:15][NH:16][C:17]2[N:26]=[C:25]([C:27]3[CH:28]=[N:29][N:30]([CH2:32][O:33][CH3:34])[CH:31]=3)[CH:24]=[C:23]3[C:18]=2[CH:19]=[CH:20][CH:21]=[N:22]3)[CH2:7][CH2:6][CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.FC(F)(F)C(O)=O>C(Cl)Cl>[F:1][C@@:2]1([CH2:15][NH:16][C:17]2[C:18]3[CH:19]=[CH:20][CH:21]=[N:22][C:23]=3[CH:24]=[C:25]([C:27]3[CH:28]=[N:29][N:30]([CH2:32][O:33][CH3:34])[CH:31]=3)[N:26]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 682098891,1-Dimethylethyl (3R)-3-fluoro-3-{[(7-{1-[(methyloxy)methyl]-1H-pyrazol-4-yl}-1,6-naphthyridin-5-yl)amino]methyl}-1-piperidinecarboxylate

Product 1

HCID 54575461N-{[(3S)-3-Fluoro-3-piperidinyl]methyl}-7-{1-[(methyloxy)methyl]-1H-pyrazol-4-yl}-1,6-naphthyridin-5-amineYield 54.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 1,1-dimethylethyl (3R)-3-fluoro-3-{[(7-{1-[(methyloxy)methyl]-1H-pyrazol-4-yl}-1,6-naphthyridin-5-yl)amino]methyl}-1-piperidinecarboxylate (813 mg, 1.728 mmol) in DCM (10 ml) was added trifluoroacetic acid (2 ml, 26.0 mmol) and stirred at room temperature for 2 h. LCMS showed product as the main peak. The solvent was removed and dissolved in methanol and loaded onto a pre-equilibrated 50 g SCX cartridge. Washed with methanol and eluted with 2M methanolic ammonia. The solvent from the ammonia fractions was removed and the residue dried under high vacuum overnight. The residue was purified on the large scale high pH MDAP (Method D). Appropriate fractions were combined and the solvent removed. The resulting product was dried under high vacuum for 1 h to give the title compound as a yellow solid (349 mg).

Workup

  1. customThe solvent was removed
  2. dissolutiondissolved in methanol
  3. washWashed with methanol
  4. washeluted with 2M methanolic ammonia
  5. customThe solvent from the ammonia fractions was removed
  6. customthe residue dried under high vacuum overnight
  7. customThe residue was purified on the large scale high pH MDAP (Method D)
  8. customthe solvent removed
  9. customThe resulting product was dried under high vacuum for 1 h

Sources & evidence

ORD record
ord-2889d8f517b3443fbbec5fa2fd6b9bc3
Source dataset
uspto-grants-2014_01
Patent number
US08633319B2

Reaction notes

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