Potassium Carbonate → 7-(4-chlorobenzyl)-8-ethoxy-3-ethyl-1-(3-hydroxypropyl)-1H-purine-2,6(3H,7H)-dione

HRID 2200688Notes

Reaction equation

[CH2:1]([O:3][C:4]1[NH:12][C:11]2[C:10](=[O:13])[N:9]([CH2:14][CH2:15][CH2:16][OH:17])[C:8](=[O:18])[N:7]([CH2:19][CH3:20])[C:6]=2[N:5]=1)[CH3:2].Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C.O>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([CH2:22][N:12]2[C:11]3[C:10](=[O:13])[N:9]([CH2:14][CH2:15][CH2:16][OH:17])[C:8](=[O:18])[N:7]([CH2:19][CH3:20])[C:6]=3[N:5]=[C:4]2[O:3][CH2:1][CH3:2])=[CH:24][CH:25]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 8-ethoxy-3-ethyl-1-(3-hydroxypropyl)-1H-purine-2,6(3H,7H)-dione (70 mg, 0.248 mmol, intermediate 26) in DMF (3 mL) was added 1-(bromomethyl)-4-chlorobenzene (80 mg, 0.390 mmol), followed by potassium carbonate (60 mg, 0.435 mmol). The mixture was stirred at 60° C. for 4 h, then diluted with ethyl acetate and water, and the phases were separated. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product which was purified by preparative HPLC to give 7-(4-chlorobenzyl)-8-ethoxy-3-ethyl-1-(3-hydroxypropyl)-1H-purine-2,6(3H,7H)-dione (15 mg, 14.9% yield) as white solid. 1H-NMR (DMSO-d6) δ 7.43-7.41(d, 2H), 7.34-7.32(d, 2H), 5.21(s, 2H), 4.53-4.44(m, 3H), 3.99-3.88(m, 4H), 3.45-3.39(m, 2H), 1.71-1.64(m, 2H), 1.37-1.33(t, 3H), 1.23-1.19(t, 3H). LCMS retention time 2.654 min; LCMS MH+ 407.

Workup

customthe phases were separated
washThe organic phase was washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customto give a crude product which
customwas purified by preparative HPLC

Sources & evidence

ORD record: ord-c010cb768d3140e3afa12fbfee7acc73
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359359B2

Reaction notes

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