Triphenylphosphine → 8-(3-((2-Methylquinolin-8-yl)oxy)propoxy)quinolin-2-amine

A 20 mL scintillation vial with a septum cap was charged with PS-PPh3 resin (Aldrich Chemical Co., Inc, 60 mg, 2.4 equiv), 8-hydroxyquinaldine (1.5 equiv) and DBAD (28 mg, 1.6 equiv) and purged by passing a stream of N2 for 45 seconds. Anhydr. THF (3 mL) was added and the contents of the vial were shaken for 5 min. Then, a solution of 3-((2-aminoquinolin-8-yl)oxy)propan-1-ol (16.7 mg/mL; 1.0 mL, 0.077 mmol) in anhydr. THF (1 mL) was added and the resulting suspension was agitated at room temperature for 8 h. Then, PS-PPh3 resin (Aldrich Chemical Co., Inc, 60 mg, 2.4 equiv) and DBAD (28 mg, 1.6 equiv) were added and the mixture was agitated at room temperature for additional 6 h. The suspension was filtered, and the resin washed with THF (3×3.0 mL). The filtrate and washings were combined and evaporated in vacuo. The residue was then treated with 6.0 mL of 4 M HCl in dioxane at room temperature for 6 h. The resulting solution was evaporated in vacuo. The residue was dissolved in 1.5 mL of a 1:1 mixture of DMSO/MeOH and purified by preparative reverse-phase HPLC. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.60 (d, 1H), 7.90 (d, 1H), 7.69 (t, 1H), 7.65 (d, 1H), 7.53 (d, 1H), 7.46 (d, 1H), 7.30 (t, 1H), 7.24 (m, 1H), 7.16 (m, 1H), 6.99 (d, 1H), 4.65 (br t, 2H), 4.48 (br t, 2H), 3.10 (s, 3H), 2.64 (m, 2H); MS (DCI/NH3) m/z 360 [M+H]+.

1. customA 20 mL scintillation vial with a septum cap
2. custompurged
3. customfor 45 seconds
4. additionTHF (3 mL) was added
5. stirringthe resulting suspension was agitated at room temperature for 8 h
6. stirringthe mixture was agitated at room temperature for additional 6 h
7. filtrationThe suspension was filtered
8. washthe resin washed with THF (3×3.0 mL)
9. customevaporated in vacuo
10. additionThe residue was then treated with 6.0 mL of 4 M HCl in dioxane at room temperature for 6 h
11. customThe resulting solution was evaporated in vacuo
12. dissolutionThe residue was dissolved in 1.5 mL of a 1:1 mixture of DMSO/MeOH
13. custompurified by preparative reverse-phase HPLC

ORDレコード

ord-5f4a86e55aaf472e824878b8e754c86a

出典データセット

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06989392B2