Theophylline → Methyl (S)-2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)propanoate

HRID 1054483Notes

Reaction equation

[CH3:1][N:2]1[C:10](=[O:11])[C:9]2[NH:8][CH:7]=[N:6][C:5]=2[N:4]([CH3:12])[C:3]1=[O:13].C([O-])([O-])=O.[K+].[K+].CS(O[C@H:25]([CH3:30])[C:26]([O:28][CH3:29])=[O:27])(=O)=O>CN(C=O)C>[CH3:1][N:2]1[C:10](=[O:11])[C:9]2[N:8]([C@@H:25]([CH3:30])[C:26]([O:28][CH3:29])=[O:27])[CH:7]=[N:6][C:5]=2[N:4]([CH3:12])[C:3]1=[O:13]

Participants

Conditions

Temperature: 20 °C

Procedure

To a suspension of 1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (20 g, 111 mmol) and K2CO3 (30.6 g, 222 mmol) in DMF (400 mL) was added (R)-methyl 2-((methylsulfonyl)oxy)propanoate (which may be synthesized according to the procedure described in PCT Pub No. WO/2005/059107 (40 g, 222 mmol). The reaction mixture was stirred at 20° C. for 20 h. The reaction mixture was then quenched with saturated NH4Cl(aq), diluted with water and extracted with CH2Cl2 (3×). The combined organic extracts were washed 3× with 10% LiCl (aq), dried over Na2SO4 and evaporated in vacuo. The residue was purified using silica gel column chromatography eluting first with PE:CH2Cl2 (1:1) followed by CH2Cl2:MeOH (50:1) to give 13.5 g (50.7 mmol, 45.7%, ee: 95%) of the (S)-product. The (S)-product was analyzed by chiral HPLC to determine it is at least 95% pure as the S-isomer (≧95% ee).

Workup

custommay be synthesized
customThe reaction mixture was then quenched with saturated NH4Cl(aq)
additiondiluted with water
extractionextracted with CH2Cl2 (3×)
washThe combined organic extracts were washed 3× with 10% LiCl (aq)
dry with materialdried over Na2SO4
customevaporated in vacuo
customThe residue was purified
washeluting first with PE
customto give 13.5 g (50.7 mmol, 45.7%, ee: 95%) of the (S)-product

Sources & evidence

ORD record: ord-47343d4365f345818a9aa16ddfeb9f0c
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394308B2

Reaction notes

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