Triethylamine → tert-Butyl 4-(3-(4-amino-5-((benzyloxy)methyl)-2-butyl-5H-pyrrolo[3,2-d]pyrimidin-7-yl)prop-2-yn-1-yl)piperazine-1-carboxylate

To a degassed solution of 5-((benzyloxy)methyl)-2-butyl-7-iodo-5H-pyrrolo[3,2-d]pyrimidin-4-amine (150 mg, 0.344 mmol) in anhydrous N,N-dimethylformamide (3 mL) under nitrogen atmosphere at room temperature was added copper(I) iodide (13 mg, 0.068 mmol), bis(triphenylphosphine)palladium(II)dichloride (27 mg, 0.038 mmol) and, finally, triethylamine (0.086 mL, 0.619 mmol). The mixture was stirred at room temperature under nitrogen atmosphere for 10 minutes and then tert-butyl 4-(prop-2-yn-1-yl)piperazine-1-carboxylate (139 mg, 0.619 mmol) was added in one portion. The reaction mixture was heated to 55° C. in a pre-heated oil bath and stirred at 55° C. for 40 minutes. The reaction was evaporated in vacuo to yield a dark brown oil. The oil was partitioned between water and dichloromethane. The organic layer was separated and the aqueous back extracted with dichloromethane. The combined organic extracts were passed through a hydrophobic frit and evaporated in vacuo to yield a dark brown oil. The oil was dissolved in MeOH:DMSO (1:1) (2×1 mL) and purified by MDAP (Method B). Appropriate fractions were combined and evaporated in vacuo to yield the title compound as a brown oil (180 mg).

1. temperatureThe reaction mixture was heated to 55° C. in a pre-heated oil bath
2. stirringstirred at 55° C. for 40 minutes
3. customThe reaction was evaporated in vacuo
4. customto yield a dark brown oil
5. customThe oil was partitioned between water and dichloromethane
6. customThe organic layer was separated
7. extractionthe aqueous back extracted with dichloromethane
8. customevaporated in vacuo
9. customto yield a dark brown oil
10. custompurified by MDAP (Method B)
11. customevaporated in vacuo

ORDレコード

ord-e0084ef530ce4d549438b2fa77273c03

出典データセット

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09428512B2