Dimethylformamide → 7-[(1R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-3-(8-methyl-8-azabicyclo[3.2.1]oct-2-en-3-yl)furo[3,2-c]pyridin-6-amine

温度

115 °C

In a two necked RB flask (50 mL), equipped with a N2 inlet, a water condenser and a magnetic stirrer, were placed 7-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-3-bromofuro[3,2-c]pyridine-6-amine (200 mg, 0.48 mmol), 8-methyl-3-(trimethylstannyl)-8-azabicyclo[3.2.1]oct-2-ene (216 mg, 0.75 mmol), tris(dibenzylideneacetone)dipalladium (100 mg, 0.11 mmol), tri-o-tolylphosphine (26 mg, 0.085 mmol), DMF (10 mL) and triethylamine (1.0 mL). This reaction mixture was heated at 114-116° C. for 4 h. TLC (10% MeOH in DCM) indicated that the starting material was consumed. DMF was removed under reduced pressure; water was added to the residue and extracted with DCM (3×10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was purified on silica gel column chromatography eluting with 2-5% methanol in dichloromethane to give the title compound. 1H NMR (CDCl3, 300 MHz): δ=1.2 (m, 1H), 2.85 (d, J=6.6 Hz, 3H), 2.31 (m, 2H), 2.58 (br, m, 2H), 2.70 (s, 3H), 3.10 (br, d, 1H), 3.90 (d, br, 2H), 4.77 (br, 2H), 6.40 (d, J=6.0 Hz, 1H), 6.55 (m, 1H), 7.01 (t, J=6.6 Hz, 1H), 7.30 (t, J=6.6 Hz, 1H), 7.40 (s, 1H), 8.21 (s, 1H).

1. customIn a two necked RB flask (50 mL), equipped with a N2 inlet, a water condenser and a magnetic stirrer
2. customwas consumed
3. customDMF was removed under reduced pressure
4. additionwater was added to the residue
5. extractionextracted with DCM (3×10 mL)
6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude material was purified on silica gel column chromatography
10. washeluting with 2-5% methanol in dichloromethane

ORDレコード

ord-6d2c479aba2642d8aeec13830fbe5111

出典データセット

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08022206B2