Reaction #1285120

Reaction equation

methyl 4-(2,3-dihydrofuran-2-yl)benzoate

bromine

2,4-diamino-6-hydroxypyrimidine

sodium acetate

→

product

Yield 47.0%

4-(1-Hydroxy-2-[2-amino-4-hydroxypyrrolopyrimidin-5-y]-ethyl)benzoic acid methyl ester

Yield 47.0%

Solvents

acetonitrile

water

acetonitrile

Conditions

Workup

1. 1
   workup.ADDITIONafter addition
2. 2
   Temperaturethe mixture was heated to about 75° C. for 2 h
3. 3
   workup.WAITAfter about 20 min the product began
4. 4
   Otherto precipitate
5. 5
   TemperatureThe mixture was cooled to room temperature
6. 6
   workup.ADDITION20 mL of water was added
7. 7
   FiltrationThe product was filtered
8. 8
   Otherdried
9. 9
   Otheraffording 2.3 g of crude product
10. 10
    OtherThe crude material was purified by slurry in DMF (140° C.)
11. 11
    Temperaturecooling
12. 12
    Filtrationfiltration
13. 13
    FiltrationFiltration of the ether suspension

Procedure

To a vigorously stirred mixture of 2.04 g (10 mmol) of methyl 4-(2,3-dihydrofuran-2-yl)benzoate in 15 mL of acetonitrile and 20 mL of water cooled to -10° C. was added dropwise a solution of 1.60 g (10 mmol) of bromine in 5 mL of acetonitrile. The mixture was stirred for 15 min after addition was complete. There was then added 1.26 g (10 mmol) of 2,4-diamino-6-hydroxypyrimidine and 2.46 g (30 mmol) of sodium acetate and the mixture was heated to about 75° C. for 2 h. After about 20 min the product began to precipitate. The mixture was cooled to room temperature and 20 mL of water was added. The product was filtered and dried, affording 2.3 g of crude product. The crude material was purified by slurry in DMF (140° C.), cooling, filtration, and reslurry in ether. Filtration of the ether suspension gave 1.54 g (47%) of the product as a white powder, mp>260° C. 1H NMR (DMSO-d6) δ2.88 (m, 2H), 3.81 (s, 3H), 4.95 (m, 1H), 5.71 (d, J=4.7 Hz, 1H), 6.03 (s, 2H), 6.21 (br d, J=1.8 Hz, 1H), 7.41 (d, J=8.3 Hz, 2H), 7.86 (d, J=8.3 Hz, 2H), 10.28 (s, 1H), 10.64 (br s, 1H); MS(FD) m/z 328 (M+). Anal. Calcd for C16H16N4O4 : C, 58.37; H, 5.04; N, 17.29. Found: C, 58.53; H, 4.91; N, 17.06.

Source