Triethylamine → HCID 178462875, compound

5-Methoxy-1H-pyrazole-3-carboxylic acid (86 mg, 0.61 mmol), 1-hydroxybenzotriazole hydrate (111 mg, 0.73 mmol) and triethylamine (253 μl, 184 mg, 1.82 mmol) were dissolved in N,N-dimethylformamide (DMF) (2 ml) and after the addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (139 mg, 0.73 mmol) dissolved in DMF (2 ml) the reaction mixture was stirred at room temperature. After 1 hour a solution of 5,6-diamino-1-ethyl-3,3-dimethyl-1,3-dihydro-indol-2-one in DMF (2 ml) was added and the reaction mixture was stirred at room temperature for 16 hours. The solvent was removed under reduced pressure, the residue was quenched with water (20 ml) and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine (15 ml), dried over sodium sulfate and evaporated. The residue was dissolved in ethanol (5 ml) and after the addition of hydrochloric acid (10 M, 2 ml) it was stirred under reflux for 2 hours. The ethanol was evaporated and the residue was adjusted to pH 9-10 with ammonium hydroxide. After the addition of water (20 ml) the aqueous phase was extracted with ethyl acetate (3×20 ml). The combined organic layers were washed with brine (10 ml), dried over sodium sulfate and evaporated. The crude product was purified by column chromatography on silica gel. Elution with ethyl acetate/n-heptane (9:1) yielded 56 mg (28%) of an off-white solid.

1. stirringthe reaction mixture was stirred at room temperature for 16 hours
2. customThe solvent was removed under reduced pressure
3. customthe residue was quenched with water (20 ml)
4. extractionextracted with ethyl acetate (3×20 mL)
5. washThe combined organic layers were washed with brine (15 ml)
6. dry with materialdried over sodium sulfate
7. customevaporated
8. dissolutionThe residue was dissolved in ethanol (5 ml)
9. additionafter the addition of hydrochloric acid (10 M, 2 ml) it
10. stirringwas stirred
11. temperatureunder reflux for 2 hours
12. customThe ethanol was evaporated
13. additionAfter the addition of water (20 ml) the aqueous phase
14. extractionwas extracted with ethyl acetate (3×20 ml)
15. washThe combined organic layers were washed with brine (10 ml)
16. dry with materialdried over sodium sulfate
17. customevaporated
18. customThe crude product was purified by column chromatography on silica gel
19. washElution with ethyl acetate/n-heptane (9:1)

ORD record

ord-69a61c56851047f7ad6c57431cea9613

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07285569B2