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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 473326
Notes
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Reaction equation

HRID 473326 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].C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

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 87.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent
HCID 6344
Dichloromethane
Solvent

Procedure

To a solution of 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 (2.24 g, 4.64 mmol) in DCM (14 ml) was added TFA (8.22 ml, 107 mmol) and this was stirred at ambient temperature for 2 h. After this time the reaction had gone to completion and so was concentrated in vacuo to yield the crude product. This was dissolved in methanol and loaded onto an SCX cartridge (50 g). It was eluted with methanol (3 CVs) and product eluted as the free base with 2M ammonia in methanol. The filtrate from the ammonia fractions was concentrated in vacuo to yield a yellow foam (1.55 g).

Workup

  1. concentrationso was concentrated in vacuo
  2. customto yield the crude product
  3. washIt was eluted with methanol (3 CVs) and product
  4. washeluted as the free base with 2M ammonia in methanol
  5. concentrationThe filtrate from the ammonia fractions was concentrated in vacuo

Sources & evidence

ORD record
ord-f1fdadb12f8b4ee28d586d238f9d58d3
Source dataset
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08633319B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes