8-Cyclopentyltheophylline → 7-(2-Chloro-6-fluorobenzyl)-8-cyclopentyl-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione

HRID 1727025Notes

Reaction equation

[CH:1]1([C:6]2[NH:14][C:13]3[C:12](=[O:15])[N:11]([CH3:16])[C:10](=[O:17])[N:9]([CH3:18])[C:8]=3[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[Cl:25][C:26]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[C:27]=1[CH2:28]Br>CN(C=O)C>[Cl:25][C:26]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[C:27]=1[CH2:28][N:14]1[C:13]2[C:12](=[O:15])[N:11]([CH3:16])[C:10](=[O:17])[N:9]([CH3:18])[C:8]=2[N:7]=[C:6]1[CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 8-cyclopentyl-1,3-dimethylxanthine (100 mg, 0.40 mmol) and K2CO3 (80 mg, 0.58 mmol) was treated with 2-chloro-6-fluorobenzyl bromide (142 mg, 0.64 mmol) dissolved in 400 μL DMF. The reaction mixture was sealed and heated to 60° C. for 24 hrs. The reaction mixture was cooled and purified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 F264) eluting with EtOAc:hexane (1:1) to give 23 mg (14% yield) of the title compound as a white solid: 1H NMR (CDCl3, 400 MHz) 7.29-7.11 (m, 2H), 7.01-6.85 (m, 1H), 5.86 (s, 2H), 3.54 (s, 3H), 3.38 (s, 3H); 3.02-2.81 (m, 1H), 1.83-1.43 (m, 8H); MS (ESP+) m/e 391 (MH+); TLC(EtOAc:hexanes/1:1) Rf=0.58.

Workup

customThe reaction mixture was sealed
temperatureThe reaction mixture was cooled
custompurified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 F264)
washeluting with EtOAc:hexane (1:1)

Sources & evidence

ORD record: ord-8b3dc563035b481ca23b1478f32cb074
Source dataset: uspto-grants-2009_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07495004B2

Reaction notes

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