Diisopropylethylamine → HCID 9821924, Verbindung

A suspension of (6-methoxy-isoquinolin-4-yl)-acetic acid (3.5 g, 13.82 mmol) in acetonitrile (70 ml) is treated sequentially with Hunig's base (6.15 ml, 36 mmol), O(7-benzotriazo-1-yl)-N,N,N′, N′-tetramethyluronium hexafluorophosphate (6.29 g, 16.6 mmol) and 5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione (3.22 g, 15.2 at mmol) while the solution is stirred at room temperature. The reaction is stirred at ambient temperature for 2 h, prior to evaporation of the solvent. The residue is triturated with ethyl acetate (50 ml) filtered and washed with ethyl acetate and then dried at 50° C. under reduced pressure. The resulting intermediate is suspended in a mixture of methanol (30 ml) and 4M aqueous sodium hydroxide (60 ml) and heated at 80° C. for 45 minutes. This suspension is neutralised with acetic acid and cooled to 0-5° C. overnight. The resultant solid is collected by filtration, and washed with methanol/water 1:9 (30 ml) followed by methanol (30 ml). Drying under high vacuum at 50° C. affords 3-isobutyl-8-(6-methoxy-isoquinolin-4-ylmethyl)-1-methyl-3,7-dihydro-purine-2,6-dione, [MH]+ 394.5.

1. stirringThe reaction is stirred at ambient temperature for 2 h
2. customto evaporation of the solvent
3. customThe residue is triturated with ethyl acetate (50 ml)
4. filtrationfiltered
5. washwashed with ethyl acetate
6. customdried at 50° C. under reduced pressure
7. additionThe resulting intermediate is suspended in a mixture of methanol (30 ml) and 4M aqueous sodium hydroxide (60 ml)
8. temperatureheated at 80° C. for 45 minutes
9. temperaturecooled to 0-5° C. overnight
10. filtrationThe resultant solid is collected by filtration
11. washwashed with methanol/water 1:9 (30 ml)
12. customDrying under high vacuum at 50° C.

ORD-Eintrag

ord-ebac3f0c6e324fa8aefce22b14df2399

Quelldatensatz

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07361661B2