Tetrahydrofuran → 1-Propyl-2-trifluoromethyl-8-[1-(3-trifluoromethyl-benzyl)-1h-pyrazol-4-yl]-1,7-dihydro-purin-6-one

HRID 536016Notes

Reaction equation

HRID 536016 reaction equation
I[C:2]1[N:3]([CH2:28][CH2:29][CH3:30])[C:4](=[O:27])[C:5]2[NH:6][C:7]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19](C(F)(F)F)[CH:18]=4)[CH:15]=3)=[N:8][C:9]=2[N:10]=1.C1COCC1.[F:36][C:37](I)([F:39])[F:38]>[Zn].CN(P(N(C)C)(N(C)C)=O)C>[CH2:28]([N:3]1[C:4](=[O:27])[C:5]2[NH:6][C:7]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([C:37]([F:39])([F:38])[F:36])[CH:18]=4)[CH:15]=3)=[N:8][C:9]=2[N:10]=[C:2]1[C:37]([F:39])([F:38])[F:36])[CH2:29][CH3:30]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 16843TrifluoroiodomethaneHCID 671347762-Iodo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one

Product 1

HCID 872829241-Propyl-2-trifluoromethyl-8-[1-(3-trifluoromethyl-benzyl)-1h-pyrazol-4-yl]-1,7-dihydro-purin-6-oneYield 14%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 12679HexamethylphosphoramideSolvent

Procedure

A mixture of 2-Iodo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one (36 mg, 0.068 mmol), Zn dust (10 mg, 0.136 mmol) and THF (2 ml) was stirred for 2 hours at room temperature. Trifluoromethyl iodide gas was passed through the reaction mixture and HMPA (2 ml) was added and heated at 120° C. for 18 hours. The reaction mixture was cooled to room temperature, organic volatile solvent was evaporated and the residue was extracted with DCM (2×10 ml). The organic layer was washed with brine (10 ml), dried over Na2SO4, evaporated and purified by preparative HPLC to get 1-Propyl-2-trifluoromethyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,7-dihydro-purin-6-one as pale yellow solid (4.5 mg, 14%).

Workup

  1. additionwas added
  2. temperatureheated at 120° C. for 18 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customorganic volatile solvent was evaporated
  5. extractionthe residue was extracted with DCM (2×10 ml)
  6. washThe organic layer was washed with brine (10 ml)
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-1d50106644694551bf68cc15a7bd6df3
Source dataset
uspto-grants-2014_10
Patent number
US08859566B2

Reaction notes

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