Diisopropylamine → 1,3-Dimethyl-2,4-dioxo-6-((2-(trimethylsilyl)ethoxy)methyl)-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-ylboronic acid

Temperature

-5 °C

Butyl lithium (1.26M, 28.4 mL, 35.8 mmol) was added dropwise to a solution of diisopropylamine (3.63 g, 35.8 mmol) in THF (20 mL) at −78° C., keeping the internal temperature below −40° C. Once the addition was complete, the contents of the flask were allowed to warm to −5° C., then were re-cooled to −78° C. The resulting mixture was cannulated over a period of about 30 minutes into a suspension of 1,3-dimethyl-6-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (step 1) (6.93 g, 22.4 mmol) in THF (75 mL) at −78° C. The mixture was stirred at −78° C. for 30 minutes, then triisopropylborate (8.3 mL, 35.8 mmol) was added dropwise. The solution was stirred at −78° C. for 1.5 hours, then was quenched by carefully adding sat ammonium chloride (200 mL). The mixture was allowed to reach room temperature and extracted with ethyl acetate (3×100 mL). The combined organic extracts were dried with magnesium sulfate and the solvent was removed under vacuum. The crude material was triturated with ether/hexane and dried under vacuum at 50° C. The solid was recombined with the mother liquor which was reduced under vacuum. The resultant semi-solid material was triturated with iso-hexane and dried under vacuum at 50° C. to afford the title compound;

1. customthe internal temperature below −40° C
2. additionOnce the addition
3. temperaturewere re-cooled to −78° C
4. stirringThe solution was stirred at −78° C. for 1.5 hours
5. customwas quenched
6. additionby carefully adding
7. customto reach room temperature
8. extractionextracted with ethyl acetate (3×100 mL)
9. dry with materialThe combined organic extracts were dried with magnesium sulfate
10. customthe solvent was removed under vacuum
11. customThe crude material was triturated with ether/hexane
12. customdried under vacuum at 50° C
13. customThe resultant semi-solid material was triturated with iso-hexane
14. customdried under vacuum at 50° C.

ORD record

ord-219e7b113f084010890fca3ed85d2ba2

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09303035B2