3-Tetrahydropyran-4-ylimidazol-4-amine → 2-amino-6-fluoro-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1850691Notes

Reaction equation

HRID 1850691 reaction equation
[NH2:1][C:2]1[C:11]([C:12]([O:14]N2C3C=C(Cl)C=CC=3N=N2)=O)=[C:5]2[N:6]=[CH:7][C:8]([F:10])=[CH:9][N:4]2[N:3]=1.[O:25]1[CH2:30][CH2:29][CH:28]([N:31]2[C:35]([NH2:36])=[CH:34][N:33]=[CH:32]2)[CH2:27][CH2:26]1>CN1C(=O)CCC1>[NH2:1][C:2]1[C:11]([C:12]([NH:36][C:35]2[N:31]([CH:28]3[CH2:29][CH2:30][O:25][CH2:26][CH2:27]3)[CH:32]=[N:33][CH:34]=2)=[O:14])=[C:5]2[N:6]=[CH:7][C:8]([F:10])=[CH:9][N:4]2[N:3]=1

Participants

4

Reactant 2

HCID 847316943-Tetrahydropyran-4-ylimidazol-4-amineHCID 86720889HCID 86720889, compound

Product 1

HCID 854725562-amino-6-fluoro-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 19.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

(6-chlorobenzotriazol-1-yl) 2-amino-6-fluoro-pyrazolo[1,5-a]pyrimidine-3-carboxylate (120.1 mg, 0.3454 mmol) and 3-tetrahydropyran-4-ylimidazol-4-amine (75 mg, 0.314 mmol) (prepared according to a procedure similar to Preparation 10) were suspended in NMP (1 mL) and stirred at 100° C. for 19 hours. The reaction was cooled to ambient temperature and purified by passing the crude reaction mixture through a 10 g SCX-2 cartridge (pre-washed with MeOH). The cartridge was washed with DCM/MeOH mixtures then the product eluted with 2M NH3 in MeOH/DCM mixtures. The solvent was removed in vacuo and the material was purified by fractionlynx. The clean fractions were freeze-dried to give title compound 2-amino-6-fluoro-N-(1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a beige solid (21.1 mg, 19% Yield). MS (ES+) 346.1.

Workup

  1. customaccording to a procedure similar to Preparation 10)
  2. temperatureThe reaction was cooled to ambient temperature
  3. custompurified
  4. customreaction mixture
  5. washthrough a 10 g SCX-2 cartridge (pre-washed with MeOH)
  6. washThe cartridge was washed with DCM/MeOH mixtures
  7. washthe product eluted with 2M NH3 in MeOH/DCM mixtures
  8. customThe solvent was removed in vacuo
  9. customthe material was purified by fractionlynx
  10. customThe clean fractions were freeze-dried

Sources & evidence

ORD record
ord-ff5b1ce856c4492183f0e96de94039bb
Source dataset
uspto-grants-2015_02
Patent number
US08957078B2

Reaction notes

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