Sulfuric acid magnesium salt (1:1) → HCID 58864221, compound

To a solution/suspension of 5-aminoindazole (1.01 g, 7.6 mmol) in tetrahydrofuran (20 mL) was added ethyl glyoxlate solution (ca. 50% in toluene, 1.7 mL, 1.1 equiv) in one portion followed by magnesium sulfate (4.6 g). The mixture was stirred at room temperature overnight (23 h) and then filtered and concentrated in vacuo. The resulting crude imine intermediate (1.3 g, 6 mmol) was dried by azeotroping with anhydrous benzene and further dried under high vacuum. The residue was then dissolved in tetrahydrofuran (20 mL) and cooled at 0° C. A solution of 2-tert-butoxy-2-oxoethylzinc chloride (0.5 M in ether, 24 mL, 2 equiv) was then slowly added. After stirring at 0° C. for 1 h, the mixture was stored at 4° C. overnight. The mixture was then diluted with ethyl acetate and quenched with half-saturated ammonium chloride solution along with a minimum amount of 0.5 N HCl to dissolve the precipitated solids. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and saturated sodium bicarbonate solution. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel, eluting with 10% methanol in methylene chloride, to afford the desired product (1.3 g, 65%) as a tan oil. 1H-NMR (400 MHz, CDCl3) δ 7.89 (1H, s), 7.40-7.27 (1H, m), 6.98-6.77 (2H, m), 4.42-4.35 (1H, m), 4.30-4.12 (3H, m), 2.80 (2H, d, J=4.4 Hz), 1.43 (9H, s), 1.27-1.17 (4H, m). Mass spec.: 356.24 (M+Na)+, 278.23 (M−tBu)+, tR=1.287 min.

1. additionwas added ethyl glyoxlate solution (ca. 50% in toluene, 1.7 mL, 1.1 equiv) in one portion
2. filtrationfiltered
3. concentrationconcentrated in vacuo
4. customby azeotroping with anhydrous benzene
5. customfurther dried under high vacuum
6. dissolutionThe residue was then dissolved in tetrahydrofuran (20 mL)
7. temperaturecooled at 0° C
8. stirringAfter stirring at 0° C. for 1 h
9. waitthe mixture was stored at 4° C. overnight
10. customquenched with half-saturated ammonium chloride solution along with a minimum amount of 0.5 N HCl
11. dissolutionto dissolve the precipitated solids
12. customThe layers were separated
13. extractionthe aqueous layer was extracted with ethyl acetate
14. washThe combined organic layers were washed with water and saturated sodium bicarbonate solution
15. dry with materialThe organic layer was dried over sodium sulfate
16. concentrationconcentrated in vacuo
17. customThe crude product was purified by flash column chromatography on silica gel
18. washeluting with 10% methanol in methylene chloride

ORD record

ord-6145ce47ac264b879728d6a3a0aec151

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07842808B2