Phenol → HCID 10216245, compound

4-Chloro-6,7-methylenedioxyquinoline. Was prepared from 4-hydroxy-6,7-methylenedioxyquinoline using methods as previous described in the literature for the conversion of 4-hydroxyquinoline to 4-chloroquinoline. Compound 5 had: mp 127.5-128° C. (Lit.28 mp 129° C.); 1H NMR (CDCl3) 6.15 (s, 2H), 7.35 (d, 1H, J=4.7), 7.39 (s, 1H), 7.49 (s, 1H), 8.56 (d, 1H, J=4.7); 13C NMR (CDCl3) 99.8, 102.2, 106.1, 119.9, 123.7, 129.8, 141.2, 147.7, 149.1, 151.4. b. N-(6,7-Methylenedioxyquinolin-4-yl)butylamine. 4-Chloro-6,7-methylenedioxyquinoline was stirred in refluxing phenol (5.5 mol equiv.) for 2.5 h. The temperature was lowered to 100° C. and butylamine (1.0 mol equiv.) was added with stirring. The reaction was then allowed to stir at 100° C. for several hours, and the phenol removed by Kugelrohr distillation under reduced pressure. The residue was partitioned between CHCl3 and 10% NaOH. The aqueous layer was repeatedly separated with CHCl3. All of the CHCl3 solutions (initial partition and extracts) were combined and dried (MgSO4), and purified by column chromatography to provide the product; mp 186-187° C.; 1H NMR (CD3OD) δ 1.02 (t, 3H, J=7.2), 1.52 (q, 2H, J=7.2), 1.75 (q, 2H J=7.2), 3.33 (q, 2H, J=7.2), 4.88 (b, 1H), 6.08 (s, 2H), 6.40 (d, 1H, J=5.6), 7.07 (s, 1H), 7.35 (s, 1H), 8.37 (d, 1H, J=6.0); 13C NMR (CH3OD) δ 12.2, 19.3, 29.6, 42.3, 96.9, 97.3, 98.8, 102.3, 112.5, 138.7, 141.5, 147.3, 151.6, 152.8; HRMS calcd for C14H16N2O2: 244.1212. Found 244.1222. c. N-(6,7-Methylenedioxyquinolin-4-yl)-N-(butyl)-2-iodo-4,5-dimethoxybenzamide. A 2.0M solution of oxalyl chloride in CH2Cl2 (8.2 mmol) was added to a solution of 2-iodo-5,6-dimethoxybenzoic acid (1.9 mmol) in anhydrous CH2Cl2 (≈60 mL per 10 mmol benzoic acid) and the solution stirred at reflux for 3 h. The mixture was allowed to cool and was then concentrated to dryness in vacuo. To the residue was added a solution of N-(6,7-Methylenedioxyquinolin-4-yl)butylamine (400 mg, 1.6 mmol), triethylamine (2 equiv.) in CH2Cl2 (≈60 mL per 4 mmol aminoquinoline). The reaction mixture was then stirred at reflux under N2 for 72 h. The residue was partitioned between CHCl3 and 10% NaOH. The aqueous layer was repeatedly separated with CHCl3. All of the CHCl3 solutions (initial partition and extracts) were combined and dried (MgSO4). The aqueous layer was neutralized with 20% NaOH and extracted with CHCl3, dried (MgSO4) and evaporated to provide the compound: 1H NMR (CDCl3) δ 0.85 (t, 3H, J=7.4), 1.20-1.91 (m, 4H), 3.22 (s, 3H), 3.65 (s, 3H), 4.45 (m, 2H), 6.08 (d, 2H, J=1.8), 6.31 (s, 1H), 6.97 (s, 1H), 7.17 (d, 1H, J=4.8), 7.29 (s, 1H), 7.30 (s, 1H), 8.49 (d, 1H, J=4.8).

1. customwas lowered to 100° C.
2. stirringto stir at 100° C. for several hours
3. customthe phenol removed by Kugelrohr distillation under reduced pressure
4. customThe residue was partitioned between CHCl3 and 10% NaOH
5. customThe aqueous layer was repeatedly separated with CHCl3
6. dry with materialdried (MgSO4)
7. custompurified by column chromatography
8. customto provide the product
9. stirringthe solution stirred
10. temperatureat reflux for 3 h
11. temperatureto cool
12. concentrationwas then concentrated to dryness in vacuo
13. stirringThe reaction mixture was then stirred
14. temperatureat reflux under N2 for 72 h
15. customThe residue was partitioned between CHCl3 and 10% NaOH
16. customThe aqueous layer was repeatedly separated with CHCl3
17. dry with materialdried (MgSO4)
18. extractionextracted with CHCl3
19. dry with materialdried (MgSO4)
20. customevaporated
21. customto provide the compound

ORD record

ord-7162fe6bffe24f4a9b0f86b7a7b4c1a9

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07319105B2