Isopropyl iodide → HCID 68831377, compound

HRID 1727022Notes

Reaction equation

HRID 1727022 reaction equation
[Br:1][C:2]1[N:10]([CH2:11][C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:19])[C:9]2[C:8](=[O:20])[N:7]([CH3:21])[C:6](=[O:22])[NH:5][C:4]=2[N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH:29](I)([CH3:31])[CH3:30]>CN(C=O)C>[Br:1][C:2]1[N:10]([CH2:11][C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:19])[C:9]2[C:8](=[O:20])[N:7]([CH3:21])[C:6](=[O:22])[N:5]([CH:29]([CH3:31])[CH3:30])[C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 57565616HCID 57565616, compound

Product 1

HCID 68831377HCID 68831377, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 8-bromo-7-(2-chloro-6-fluorobenzyl)-1-methyl-3,7-dihydro-1H-purine-2,6-dione (67 mg, 0.17 mmol) and K2CO3 (239 mg, 1.7 mmol) in 1.7 mL DMF was treated with isopropyl iodide (85 μL, 0.86 mmol). The reaction was stirred at room temperature for 15 hr. The reaction mixture was filtered through a silica plug and rinsed with EtOAc. The solvent was removed under reduced pressure and the crude product was purified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 F264) eluting with EtOAc:hexane (1:3) to give 46 mg (63% yield) of 8-bromo-7-(2-chloro-6-fluorobenzyl)-3-isopropyl-1-methyl-3,7-dihydro-1H-purine-2,6-dione. A solution of this intermediate (45 mg, 0.11 mmol) in 110 μL aqueous sodium carbonate (2 M), 270 μL toluene, and 45 μL ethanol was treated with 3-chlorophenylboronic acid (18 mg, 0.12 mmol), tetrakis(triphenylphosphine)palladium(0) (3.6 mg, 0.0032 mmol), and lithium chloride (catalytic). The reaction mixture was heated to 100° C. in a sealed vial and stirred overnight. The reaction mixture was cooled, filtered through a silica plug, and rinsed with 50% EtOAc:hexanes. The solvent was removed under reduced pressure and the crude product was purified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 h64) eluting with ether:hexane (1:1) to give 38 mg (77% yield) of the title compound as a white solid: 1H NMR (CDCl3, 400 MHz) 7.41-7.37 (m, 1H), 7.37-7.22 (m, 3H), 7.13-7.06 (m, 1H), 7.05-7.00 (m, 1H), 6.82-6.74 (m, 1H), 5.86 (s, 2H), 5.25-5.13 (m, 1H), 3.35 (s, 3H), 1.58 (d, 6H, J=7); MS (ESP+) m/e 461 (MH+); TLC (ether:hexanes/1:1) Rf=0.37.

Workup

  1. filtrationThe reaction mixture was filtered through a silica plug
  2. washrinsed with EtOAc
  3. customThe solvent was removed under reduced pressure
  4. customthe crude product was purified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 F264)
  5. washeluting with EtOAc:hexane (1:3)

Sources & evidence

ORD record
ord-af686c234e184218ad12934394e73cc6
Source dataset
uspto-grants-2009_02
Patent number
US07495004B2

Reaction notes

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