Cesium carbonate → HCID 67086679, compound

Temperature

100 °C

To a 100 ml round bottom flask containing 2-chloro-6-methylnicotinic acid (3 g, 17.4 mmol), copper iodide (0.16 g, 0.5 mol %), and cesium carbonate (11.4 g, 35 mmol) was added a mixture of dioxane (20 mL) and H2O (0.1 ml, 5.25 mmol). Next triazole (2.03 mL, 35 mmol) and finally (R,R)-(−)-N,N′-dimethyl-1,2-cyclohexanediamine ligand (0.56 mL, 3.5 mmol) were added. The resulting clumpy yellow slurry was stirred until evenly dispersed. Upon heating to 100° C. the reaction mixture changed from a yellow slurry to pale green. As heating progressed the slurry became less thick and was stirred more easily. The light green slurry was stirred for 4 hr at 100° C. and left to stir at room temp overnight. At this point the reaction mixture appeared as a cobalt blue slurry which was then diluted with 20 mL ether and 20 mL H2O. The resulting solution was thoroughly stirred and transferred to a seperatory funnel then the RBF was subsequently rinsed with 20 mL ether and H2O each. The aqueous layer was separated from the organic layer and acidified to pH 1 with 6 mL conc. HCl. The now brown/lime green aqueous layer was extracted twice with EtOAc. The bright yellow organic layers were combined and dried with Na2SO4 and then conc. into a yellow powder under reduced pressure. To the yellow powder was added EtOAc to form a yellow slurry. The solids were filtered off and washed with EtOAc to give a very pale yellow powder, which was found by 1H NMR to be Intermediate 53 (25% yield). The filtrate was conc. into a yellow solid and purified by FCC using 0-5% MeOH in DCM w/0.5% AcOH to give the title compound in a 20% yield. MS (ESI): mass calculated for C9H8N4O2, 204.18; m/z found 205.3 [M+H]+. 1H NMR (400 MHz, CD3OD): 8.21-8.18 (m, 1H), 7.98 (s, 2H), 7.51 (d, J=7.9 Hz, 1H), 2.64 (s, 3H).

1. additionwas added
2. additionuntil evenly dispersed
3. temperatureAs heating
4. stirringwas stirred more easily
5. stirringThe light green slurry was stirred for 4 hr at 100° C.
6. waitleft
7. stirringto stir at room temp overnight
8. stirringThe resulting solution was thoroughly stirred
9. customtransferred to a seperatory funnel
10. washthe RBF was subsequently rinsed with 20 mL ether and H2O each
11. customThe aqueous layer was separated from the organic layer
12. extractionThe now brown/lime green aqueous layer was extracted twice with EtOAc
13. dry with materialdried with Na2SO4
14. additionTo the yellow powder was added EtOAc
15. customto form a yellow slurry
16. filtrationThe solids were filtered off
17. washwashed with EtOAc
18. customto give a very pale yellow powder, which

ORD record

ord-60e96a4aaf9341a9af794af78881a012

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062044B2