Trifluoroacetic acid → 5-(2-(2-azabicyclo[2.1.1]hexan-2-yl)-6-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)pyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-amine

HRID 1778175Notes

Reaction equation

HRID 1778175 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([N:14]3[CH2:18][CH:17]4[CH2:19][CH:15]3[CH2:16]4)[N:11]=[C:10]([N:20]3[CH2:25][C@@H:24]4[CH2:26][C@H:21]3[CH2:22][N:23]4C(OC(C)(C)C)=O)[CH:9]=2)=[CH:4][C:3]=1[C:34]([F:37])([F:36])[F:35].FC(F)(F)C(O)=O>ClCCl>[CH:15]12[CH2:16][CH:17]([CH2:19]1)[CH2:18][N:14]2[C:12]1[N:13]=[C:8]([C:5]2[CH:4]=[C:3]([C:34]([F:37])([F:36])[F:35])[C:2]([NH2:1])=[N:7][CH:6]=2)[CH:9]=[C:10]([N:20]2[CH2:25][C@@H:24]3[CH2:26][C@H:21]2[CH2:22][NH:23]3)[N:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117678157HCID 117678157, compound

Product 1

HCID 1176783475-(2-(2-azabicyclo[2.1.1]hexan-2-yl)-6-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)pyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-amineYield 76.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of (1S,4S)-tert-butyl 5-(6-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-2-(2-azabicyclo[2.1.1]hexan-2-yl)pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (130 mg, 0.25 mmol) in dichloromethane (6 mL) was added trifluoroacetic acid (3 mL). The mixture was stirred at room temperature for 0.5 h. After removal of the solvent, the residue was dissolved with water (30 mL), basified and extracted with dichloromethane (3×30 mL). The organic layer was dried over sodium sulfate, concentrated to provide 5-(2-(2-azabicyclo[2.1.1]hexan-2-yl)-6-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)pyrimidin-4-yl)-3-(trifluoromethyl)pyridin-2-amine (80 mg, 75.0% yield). LCMS (ESI): [MH]+=417.9.

Workup

  1. customAfter removal of the solvent
  2. dissolutionthe residue was dissolved with water (30 mL)
  3. extractionextracted with dichloromethane (3×30 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-40ef1de3f560418f9d2077337fddf861
Source dataset
uspto-grants-2016_02
Patent number
US09266862B2

Reaction notes

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