Sodium Dithionite → (R)-tert-Butyl(1-(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazole-5-carbonyl)piperidin-3-yl)carbamate

A solution of 1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (2 g, 8.99 mmol) in ethanol (90 mL) was added to a round bottom flask containing (R)-tert-butyl(1-(4-(methylamino)-3-nitrobenzoyl)piperidin-3-yl)carbamate (3.4 g, 8.98 mmol) and the resulting solution stirred at room temperature. A solution of sodium dithionite (3.14 g, 15.33 mmol) in water (45 mL) was added portionwise to the reaction mixture. The reaction mixture was heated to 100° C. and stirred under nitrogen for 4 hours. The reaction mixture was concentrated under vacuum then diluted with DCM (150 ml) and water (150 ml). The organic layer was collected and the aqueous layer washed with DCM (3×100 ml). Organic layers were collected and backwashed with water (2×100 ml). The organic layer was collected, dried with Na2SO4, filtered through a hydrophobic frit and concentrated under vacuum to yield a crude product. This was dissolved in a minimum volume of DCM and purified using Biotage SP4 on a 100 g SNAP silica cartridge. The column was eluted with a gradient of 70-100% ethyl acetate in DCM for 10CV. Appropriate fractions were collected and concentrated under vacuum. This was dried under vacuum to yield the title compound as a yellow solid (1.867 g).

1. temperatureThe reaction mixture was heated to 100° C.
2. stirringstirred under nitrogen for 4 hours
3. concentrationThe reaction mixture was concentrated under vacuum
4. additionthen diluted with DCM (150 ml) and water (150 ml)
5. customThe organic layer was collected
6. washthe aqueous layer washed with DCM (3×100 ml)
7. customOrganic layers were collected
8. customThe organic layer was collected
9. dry with materialdried with Na2SO4
10. filtrationfiltered through a hydrophobic frit
11. concentrationconcentrated under vacuum
12. customto yield a crude product
13. custompurified
14. washThe column was eluted with a gradient of 70-100% ethyl acetate in DCM for 10CV
15. customAppropriate fractions were collected
16. concentrationconcentrated under vacuum
17. customThis was dried under vacuum

ORDレコード

ord-e2877024da094255a9395671e7e3ee82

出典データセット

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09127003B2