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

HRID 473325
Notes
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Reaction equation

HRID 473325 reaction equation
[CH3:1][C:2]([N:5]1[CH:9]=[C:8]([C:10]2[CH:19]=[C:18]3[C:13]([CH:14]=[CH:15][CH:16]=[N:17]3)=[C:12]([NH:20][CH2:21][C@:22]3([F:35])[CH2:27][CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23]3)[N:11]=2)[CH:7]=[N:6]1)([CH3:4])[CH3:3].FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:4][C:2]([N:5]1[CH:9]=[C:8]([C:10]2[N:11]=[C:12]([NH:20][CH2:21][C@:22]3([F:35])[CH2:27][CH2:26][CH2:25][NH:24][CH2:23]3)[C:13]3[CH:14]=[CH:15][CH:16]=[N:17][C:18]=3[CH:19]=2)[CH:7]=[N:6]1)([CH3:1])[CH3:3]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 682099451,1-Dimethylethyl (3R)-3-[({7-[1-(1,1-dimethylethyl)-1H-pyrazol-4-yl]-1,6-naphthyridin-5-yl}amino)methyl]-3-fluoro-1-piperidinecarboxylate

Product 1

HCID 545754607-(1-tert-butyl-1H-pyrazol-4-yl)-N-{[(3S)-3-fluoropiperidin-3-yl]methyl}-1,6-naphthyridin-5-amineYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

1,1-Dimethylethyl (3R)-3-[({7-[1-(1,1-dimethylethyl)-1H-pyrazol-4-yl]-1,6-naphthyridin-5-yl}amino)methyl]-3-fluoro-1-piperidinecarboxylate (1.586 g, 3.29 mmol) was dissolved in DCM (5 ml) and trifluoroacetic acid (5.06 ml, 65.7 mmol) was added. The reaction was stirred for 20 min at 20° C. LCMS showed main peak of product. The reaction mixture was loaded onto a 20 g SCX cartridge and washed with methanol. The compound was eluted with 2M methanolic ammonia. The solvent from the ammonia fractions was evaporated and was kept under high vacuum for 2 h to give a yellow crystalline solid (1.171 g). The free base (1.12 g) was purified by High pH preparative MDAP (Method B). The appropriate fractions were combined, concentrated in vacuo and kept on high vacuum overnight to give the title compound as a yellow crystalline solid (688.1 mg).

Workup

  1. washwashed with methanol
  2. washThe compound was eluted with 2M methanolic ammonia
  3. customThe solvent from the ammonia fractions was evaporated
  4. waitwas kept under high vacuum for 2 h

Sources & evidence

ORD record
ord-7aadbfa6c0d14ad1805a1529f4ac0fac
Source dataset
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08633319B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes