Sodium Iodide → Phosphoric acid di-tert-butyl ester 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester

HRID 1429719Notes

Reaction equation

HRID 1429719 reaction equation
[O:1]=[C:2]1[N:10]([CH2:11][CH2:12][CH3:13])[C:9]([C:14]#[N:15])=[N:8][C:7]2[N:6]=[C:5]([C:16]3[CH:17]=[N:18][N:19]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=4)[CH:20]=3)[NH:4][C:3]1=2.C([O-])([O-])=O.[K+].[K+].[Na+].[I-].Cl[CH2:41][O:42][P:43](=[O:54])([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46]>CC(C)=O>[C:14]([C:9]1[N:10]([CH2:11][CH2:12][CH3:13])[C:2](=[O:1])[C:3]2[N:4]([CH2:41][O:42][P:43](=[O:54])([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[O:44][C:45]([CH3:48])([CH3:46])[CH3:47])[C:5]([C:16]3[CH:17]=[N:18][N:19]([CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=4)[CH:20]=3)=[N:6][C:7]=2[N:8]=1)#[N:15]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 11701630Di-tert-butyl (chloromethyl) phosphateHCID 668035696-Oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purine-2-carbonitrile

Product 1

HCID 66803567Phosphoric acid di-tert-butyl ester 2-cyano-6-oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-1,6-dihydro-purin-7-ylmethyl ester

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of 6-Oxo-1-propyl-8-[1-(3-trifluoromethyl-benzyl)-1H-pyrazol-4-yl]-6,7-dihydro-1H-purine-2-carbonitrile (0.5 g, 0.0012 mol), K2CO3 (0.485 g, 0.0036 mol) and acetone (10 ml) were taken and stirred for 20 minutes at room temperature. NaI (0.702 g, 0.0047 mol) was added and then Phosphoric acid di-tert-butyl ester chloromethyl ester (0.619 g, 0.0024 mol in 2 ml acetone) was added to the reaction mixture drop wise. The reaction mixture was heated at 45° C. for 16 h. The reaction mixture was filtered through celite and washed with acetone. The organic layer was concentrated and the residue was taken in ethyl acetate (30 ml) and saturated NaHCO3 solution (20 ml). The organic layer was separated and washed with saturated sodium thiosulphate solution (20 ml). The organic layer was washed with 0.5 N HCl solution (20 ml) and brine solution (20 ml). The organic layer was dried over sodium sulphate and evaporated to obtain brown colored mass. The crude product, which is a mixture of N7 and N9 isomers was purified by column chromatography (230-400 mesh silica gel and it was first treated with 5% triethyl amine in hexane) using 5-20% acetone in hexane (with 0.5 to 1% triethyl amine) as an eluent to obtain N7 isomer (0.34 g, 45%) and N9 isomer (0.11 g, 14%)

Workup

  1. temperatureThe reaction mixture was heated at 45° C. for 16 h
  2. filtrationThe reaction mixture was filtered through celite
  3. washwashed with acetone
  4. concentrationThe organic layer was concentrated
  5. customThe organic layer was separated
  6. washwashed with saturated sodium thiosulphate solution (20 ml)
  7. washThe organic layer was washed with 0.5 N HCl solution (20 ml) and brine solution (20 ml)
  8. dry with materialThe organic layer was dried over sodium sulphate
  9. customevaporated
  10. customto obtain brown colored mass
  11. additiona mixture of N7 and N9 isomers
  12. customwas purified by column chromatography (230-400 mesh silica gel and it
  13. additionwas first treated with 5% triethyl amine in hexane)
  14. customto obtain N7 isomer (0.34 g, 45%) and N9 isomer (0.11 g, 14%)

Sources & evidence

ORD record
ord-bafd902a2e76470a8ca745b044ad2846
Source dataset
uspto-grants-2015_01
Patent number
US08940751B2

Reaction notes

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