2,2-Dimethoxypropane → HCID 66743896, compound

Temperature

100 °C

A mixture of 5-bromo-3-[(pyridin-3-ylmethyl)amino]thiophene-2-carboxamide (175 mg, 0.56 mmol), 2,2-dimethoxypropane (1.5 mL), CSA (13 mg, 0.056 mmol), MgSO4 (150 mg) and DMA (1.5 mL) was microwave-irradiated at 120° C. for 1 h. The mixture was poured into saturated aqueous NaHCO3. 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 solid was obtained. A flask was charged with this solid, 1,2-dimethoxyethane (5.0 mL), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (518 mg, 1.68 mmol), sodium carbonate (168 mg, 2.80 mmol) and water (2.5 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (41 mg, 0.056 mmol) was added to the mixture. The flask was purged with argon. After stirring at 100° C. for 1 h, 8 M aqueous NaOH (1.0 mL) was added. After stirring at 100° C. for 1 h, the organic materials were extracted with EtOAc/THF. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH), then crystallized from MeOH/EtOAc) to give the title compound (64 mg, 32%, 3 steps) as a pale yellow solid:

1. customwas microwave-irradiated at 120° C. for 1 h
2. extractionThe organic materials were extracted with EtOAc
3. washThe combined extracts were washed with water and brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customAfter removal of the solvent at reduced pressure
7. customa brown solid was obtained
8. customThe flask was purged with argon
9. customThe flask was purged with argon
10. addition8 M aqueous NaOH (1.0 mL) was added
11. stirringAfter stirring at 100° C. for 1 h
12. extractionthe organic materials were extracted with EtOAc/THF
13. washThe combined extracts were washed with brine
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. customAfter removal of the solvent at reduced pressure
17. customthe residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc
18. customto 90:10 EtOAc/MeOH), then crystallized from MeOH/EtOAc)

ORD record

ord-b989e7d2f37042bfab60a44f96b61d29

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2