Oxalyl chloride → 3-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoylamino]-6,6-dimethyl-4H,6H-pyrrolo[3,4-c]pyrazole-2,5-dicarboxylic acid 5-tert-butyl ester 2-ethyl ester

温度

0 °C

To a suspension of 2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-benzoic acid (1.35 g, 4.8 mmol) in dry dichloromethane (30 mL), at 0° C., under stirring, was added oxalyl chloride (2.1 mL, 24 mmol) and dry N,N-dimethylformamide (35 microL). The mixture was allowed to warm to room temperature, stirred for 1.5 hours then evaporated to dryness. The residue was diluted with dry toluene and evaporated again. The crude acyl chloride thus obtained (yellow solid) was dissolved in dry tetrahydrofuran (20 mL) and treated with N,N-diisopropylethylamine (2.5 mL, 15 mmol) and with a solution of 3-amino-6,6-dimethyl-4H,6H-pyrrolo[3,4-c]pyrazole-2,5-dicarboxylic acid 5-tert-butyl ester 2-ethyl ester (1.3 g, 4 mmol) in 15 mL of dry tetrahydrofuran. The mixture was stirred at room temperature for 2 days then evaporated to dryness. The residue was dissolved in dichloromethane, washed with 1N HCl, water, saturated solution of NaHCO3, brine, dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel using dichloromethane/methanol 98.5:1.5 as the eluant affording the title compound as white solid (1.5 g).

1. temperatureto warm to room temperature
2. stirringstirred for 1.5 hours
3. customthen evaporated to dryness
4. additionThe residue was diluted with dry toluene
5. customevaporated again
6. customThe crude acyl chloride thus obtained (yellow solid)
7. stirringThe mixture was stirred at room temperature for 2 days
8. customthen evaporated to dryness
9. dissolutionThe residue was dissolved in dichloromethane
10. washwashed with 1N HCl, water, saturated solution of NaHCO3, brine
11. dry with materialdried over sodium sulfate
12. customevaporated to dryness
13. customThe crude was purified by flash chromatography on silica gel

ORDレコード

ord-a4ef837368814048ad7d45468327fdf3

出典データセット

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08461193B2