Ethylenediamine → 5-(1H-Indol-2-yl)-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (1-benzyl-1H-pyrazol-4-yl)-amide

Intermediate (1d), 2-[5-(1-benzyl-1H-pyrazol-4-ylcarbamoyl)-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]indole-1-carboxylic acid tert-butyl ester (315 mg, 0.492 mmol) was stirred in tetrahydrofuran (15 mL) and 1,2-diaminoethane (89 mg, 98 ul, 1.48 mmol) was added followed by tetrabutylammonium fluoride solution 1.0M in tetrahydrofuran (2.46 mL, 2.46 mmol). The reaction mixture was heated at reflux for 18 hours, and cooled to ambient temperature. The reaction mixture was concentrated in vacuo. The residue was partitioned between water and dichloromethane, and the organic layer was separated. The aqueous was extracted with a further portion of dichloromethane and the combined dichloromethane layers were washed with water (×3) dried (Na2SO4) and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 eluting with dichloromethane—8% methanol/dichloromethane (gradient) to afford a solid. This solid was triturated with diethyl ether to afford the desired title compound as a yellow solid, 41 mg, 20%.

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 18 hours
3. concentrationThe reaction mixture was concentrated in vacuo
4. customThe residue was partitioned between water and dichloromethane
5. customthe organic layer was separated
6. extractionThe aqueous was extracted with a further portion of dichloromethane
7. washthe combined dichloromethane layers were washed with water (×3)
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated in vacuo
10. customThe resultant crude product was purified by flash chromatography on SiO2 eluting with dichloromethane—8% methanol/dichloromethane (gradient)
11. customto afford a solid
12. customThis solid was triturated with diethyl ether

ORD 기록

ord-d4187dc170aa43e782be01ccb4aabe04

출처 데이터셋

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08916591B2