Trifluoroacetic acid → 1-(Azetidin-2-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine

HRID 1778435Notes

Reaction equation

HRID 1778435 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:25][CH:26]3[CH2:29][CH2:28][N:27]3C(OC(C)(C)C)=O)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][C:12]=3[F:24])[C:3]=12.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:27]1[CH2:28][CH2:29][CH:26]1[CH2:25][N:8]1[C:4]2=[N:5][CH:6]=[N:7][C:2]([NH2:1])=[C:3]2[C:10]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:13][C:12]=2[F:24])=[N:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90001120Tert-butyl 2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carboxylate

Product 1

HCID 900012121-(Azetidin-2-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amineYield 70.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the crude tert-butyl 2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carboxylate (800 mg, 1.63 mmol) dissolved in DCM (4 mL) in ice bath, was dropwise added TFA (2 mL) slowly, stirring for 10 min at which point nostarting material remained by TLC analysis. The solvent was removed and EtOAc added, which was washed with 2M HCl. The combined aq. solution was adjusted with NaOH to pH around 10, and the aq. layer extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, and the solvent removed to get 450 mg of 1-(azetidin-2-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine, which was used in the next step directly without further purification.

Workup

  1. customThe solvent was removed
  2. additionEtOAc added
  3. washwhich was washed with 2M HCl
  4. extractionthe aq. layer extracted with EtOAc
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. customthe solvent removed

Sources & evidence

ORD record
ord-5b721789cfbe4ad98e7b21e4df58c5fc
Source dataset
uspto-grants-2016_02
Patent number
US09266895B2

Reaction notes

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