Diisopropylamine → HCID 18675576, compound

Temperature

0 °C

To a stirring solution of diisopropylamine (3.72 mL, 28.35 mmol) in anhydrous THF (75 mL) at −78° C. was added 11.4 mL of a 2.5M solution of n-butyllithium in hexanes. The solution was allowed to warm to 0° C., then cooled back down to −78° C. A solution of 1-cyano-2-ethylbutane (3 g, 27 mmol) in anhydrous THF (15 mL) was added to the cooled solution. After stirring for 10 min., ethyl formate (2.7 mL, 32.4 mmol) was added and the resulting reaction mixture was stirred at −78° C. for 1 h, then allowed to slowly warm to room temperature over 3 h. The reaction mixture was then partitioned between Et2O and water. The organic layer was washed with water and the aqueous layers were combined and acidified with 1N HCl. The resulting acidic aqueous mixture was extracted with Et2O. The organic layer was washed with brine, dried over Na2SO4, filtered and evaporated in vacuo to yield a colorless oil. This residue was dissolved in ethanol (15 mL) and to the resulting solution was added water (10 mL), thiosemicarbazide (2.71 g, 29.7 mmol), and acetic acid (5.5 mL). The resulting mixture was stirred under reflux for 3 hr., then cooled and diluted with water (25 mL). The off-white precipitate which formed was collected by vacuum filtration to yield 4.7 g of the 5-amino-1-thiocarbamoylpyrazole. 1H NMR (300 mHz, CDCl3): δ7.2 (bs, 1H), 7.17 (d, 1H, J=4.4 Hz), 6.37 (bs, 1H), 3.65 (t, 1H, J=4.4, 4.8 Hz), 1.71 (m, 1H), 1.53 (m, 4H), 0.97 (m, 6H). Spectrum corresponds to imine tautomer. 1H NMR (300 mHz, dmso-d6): δ8.3 (bs, 1H), 7.4 (bs, 1H), 7.36 (d, 1H, J=4.8 Hz), 3.93 (t, 1H, J=5.13, 4.8 Hz), 1.76 (m, 1H), 1.4 (m, 4H), 0.89 (m, 6H). Spectrum corresponds to imine tautomer.

1. temperaturecooled back down to −78° C
2. customthe resulting reaction mixture
3. stirringwas stirred at −78° C. for 1 h
4. temperatureto slowly warm to room temperature over 3 h
5. customThe reaction mixture was then partitioned between Et2O and water
6. washThe organic layer was washed with water
7. extractionThe resulting acidic aqueous mixture was extracted with Et2O
8. washThe organic layer was washed with brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customevaporated in vacuo
12. customto yield a colorless oil
13. stirringThe resulting mixture was stirred
14. temperatureunder reflux for 3 hr
15. temperature, then cooled
16. customThe off-white precipitate which formed
17. filtrationwas collected by vacuum filtration

ORD record

ord-6159295b4dd8433788c9f7b9a103df55

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06509338B1