2,2-Dimethoxypropane → Cdc7-IN-15

Temperature

90 °C

A mixture of 3-amino-5-bromothiophene-2-carboxamide (1.99 g, 9.0 mmol), 2,2-dimethoxypropane (10 mL), CSA (209 mg, 0.90 mmol), MgSO4 (2.17 g, 18 mmol) and DMA (10 mL) was stirred at 90° C. for 2 h. After removal of MgSO4 by filtration, saturated aqueous NaHCO3 was added to the filtrate. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, a brown crystalline solid was obtained. A flask was charged with this solid, tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (6.0 g, 19.5 mmol), sodium carbonate (2.3 g, 38.3 mmol), 1,2-dimethoxyethane (30 mL) and water (15 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (626 mg, 0.766 mmol) was added to the mixture. The flask was purged with argon again. After stirring at 100° C. for 3.5 h, 8 M aqueous NaOH (2.0 mL) was added. After stirring at 100° C. for 1 h, the organic materials were extracted with EtOAc/THF. The combined extracts were dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, EtOAc to 90:10 EtOAc/MeOH) to give the title compound (1.97 g, 86%) as a brown solid:

1. customAfter removal of MgSO4
2. filtrationby filtration, saturated aqueous NaHCO3
3. additionwas added to the filtrate
4. extractionThe organic materials were extracted with EtOAc
5. washThe combined extracts were washed with water and brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customAfter removal of the solvent at reduced pressure
9. customa brown crystalline solid was obtained
10. customThe flask was purged with argon
11. customThe flask was purged with argon again
12. stirringAfter stirring at 100° C. for 3.5 h
13. addition8 M aqueous NaOH (2.0 mL) was added
14. stirringAfter stirring at 100° C. for 1 h
15. extractionthe organic materials were extracted with EtOAc/THF
16. dry with materialThe combined extracts were dried over Na2SO4
17. filtrationfiltered
18. customAfter removal of the solvent at reduced pressure
19. customthe residue was purified by column chromatography (Purif, silica gel, EtOAc to 90:10 EtOAc/MeOH)

ORD record

ord-1b0d14fe1cef4c11a847ffbd1c845032

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2