Diisopropylethylamine → (5R)-5-ethyl-5-methyl-3-[6-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxy-3-pyridyl]imidazolidine-2,4-dione

To a solution of triphosgene (30 mg, 0.1 mmol) in dry DCM (1 ml) at 0° C., under nitrogen atmosphere, DIPEA (0.175 ml, 1.0 mmol) was added followed by the addition (slowly added) of a solution of 6-(7-methylspiro[2H-benzofuran-3,1′-cyclopropane]-4-yl)oxypyridin-3-amine (Intermediate 15, 27 mg, 0.1 mmol) in dry DCM (2 ml) and the reaction mixture was stirred for 15 minutes at the sane temperature. After that a solution of Methyl (R)-2-amino-2-methyl-butyrate hydrochloride (33 mg, 0.2 mmol) in dry DCM (2 ml) was added and the reaction mixture was stirred for 30 minutes at 0° C. The reaction was quenched with a 1M aqueous solution of HCl (5 ml), diluted with DCM (10 ml) and two phases were separated. The organic layer was washed with brine (10 ml), dried (Na2SO4), filtered and evaporated affording the urea intermediate as yellow foam.

1. additionfollowed by the addition (
2. stirringthe reaction mixture was stirred for 30 minutes at 0° C
3. customThe reaction was quenched with a 1M aqueous solution of HCl (5 ml)
4. additiondiluted with DCM (10 ml) and two phases
5. customwere separated
6. washThe organic layer was washed with brine (10 ml)
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. customevaporated

ORDレコード

ord-27522d2bfec545d6a9ed31361116029f

出典データセット

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09133175B2