Triisopropyl borate → (6-(2-((tert-Butoxycarbonyl)amino)ethyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)boronic acid

Temperature

-78 °C

2-(1,3-Dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrrolo[3,4-d]pyrimidin-6-yl)-ethyl]-carbamic acid tert-butyl ester (step 3) (1.8 g, 5.58 mmol) was dissolved in anhydrous THF (49 ml) at room temperature. The flask was then evacuated and backfilled with nitrogen (×3) and cooled to −78° C. (external). After 10 mins, LDA (0.731 M, 22.92 ml, 16.75 mmol in THF, freshly prepared by standard procedure from BuLi and diisopropylamine) was charged over 3 mins. After 15 mins at −78° C., triisopropyl borate (3.87 ml, 16.75 mmol) was charged drop wise over 2 mins and the reaction held for 2 hr at −78° C. The reaction was then quenched with saturated NH4Cl solution (10 mL) via syringe under nitrogen and diluted with water (60 mL) and EtOAc (40 mL). The layers were separated and the aqueous extracted with EtOAc (4×50 mL). The combined organics were washed with brine (20 mL), dried (Na2SO4) and filtered under reduced pressure to afford a pale yellow solution. The solvent volume reduced by half under reduced pressure to afford a suspension of a white solid. The solid was recovered by reduced pressure filtration and dried in air, followed by heating to 50° C. under vacuum for 3 h. This afforded the title compound as a white crystalline solid.

1. customThe flask was then evacuated
2. customLDA (0.731 M, 22.92 ml, 16.75 mmol in THF, freshly prepared by standard procedure from BuLi and diisopropylamine)
3. additionwas charged over 3 mins
4. waitAfter 15 mins at −78° C.
5. waitthe reaction held for 2 hr at −78° C
6. customThe reaction was then quenched with saturated NH4Cl solution (10 mL) via syringe under nitrogen
7. additiondiluted with water (60 mL) and EtOAc (40 mL)
8. customThe layers were separated
9. extractionthe aqueous extracted with EtOAc (4×50 mL)
10. washThe combined organics were washed with brine (20 mL)
11. dry with materialdried (Na2SO4)
12. filtrationfiltered under reduced pressure
13. customto afford a pale yellow solution
14. customto afford
15. additiona suspension of a white solid
16. filtrationThe solid was recovered by reduced pressure filtration
17. customdried in air
18. temperatureby heating to 50° C. under vacuum for 3 h

ORD record

ord-0c92763accde4446802349982e3ae5bd

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09303035B2