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With 1,8-diazabicyclo[5.4.0]undec-7-ene;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃; for 6h;
Preparation of 4-(2-[(3-chlorophenyl)aminoipyrimidin-4-yl}-N-[3-(2-oxoazepan-1 - yl)propylipyridine-2-carboxamide (Compound A-D according to process P1A200 mg of N-(3-chlorophenyl)-4-(2-chloropyridin-4-yl)pyrimidin-2-amine (0.63 mmol), 332 mg of1 -(3-aminopropyl)azepan-2-one (1.89 mmol), 166 mg of molybdenum hexacarbonyl(0.631 mmol), 0.282ml of 1 ,8-Diazabicyclo(5.4.0)undec-7-ene (1.89 mmol) and 72.9 mg (0.063 mmol) of Tetrakis(triphenylphosphine)palladium(0) were diluted in 3 ml of N, N- dimethylformamide. The reaction mixture was stirred at 100C for 6 hours. After cooling, the reaction mixture was poured into 50 ml of HCI 1 M. The precipitate which formed was filtered, washed with NaOH 1 M and then water. The crude product was chromatographed on silica (ethyl acetate / heptane) to yield 0.14g of 4-{2-[(3-chlorophenyl)amino]pyrimidin-4-yl}-N-[3-(2- oxoazepan-1 -yl)propyl]pyridine-2-carboxamide (yield = 46%). [M + 1] = 479.
4-chloro-3-nitro-N-furfurylbenzenesulfonamide[ No CAS ]
4-[N-(3'-aminopropyl)-2-azepanone]-3-nitro-N-furfurylbenzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dimethyl sulfoxide; at 85℃;
General procedure: p-Chloro-N-alkylbenzenesulfonamides (1-8) (1 equiv.) andaminolactam N-(3-aminopropyl)-2-pyrrolidinone (APP)(1.25 equiv.) or <strong>[24566-95-8]N-(3-aminopropyl)-2-azepanone</strong> (<strong>[24566-95-8]APA</strong>)(1.25 equiv.) were added to a 50 mL round-bottomed flaskand dissolved in dimethylsulfoxide (10 mL) for a nucleophilicaromatic substitution reaction (SNAr). The contents were then stirred in a reflux system for 1-2 h at 85 C.Afterward, the solvent was removed with frozen water andthe product was treated with diluted HCl (5 %) for removalof amino-lactam excess. The crude product was filtered offand recrystallized from 1:1 ethyl ether-petroleum ether (bp60-80 C). All obtained compounds were structurally confirmedby 13C and 1H NMR analyses (see Supplementarymaterial).
4-chloro-3-nitro-N-benzylbenzenesulfonamide[ No CAS ]
4-[N-(3'-aminopropyl)-2-azepanone]-3-nitro-N-benzylbenzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dimethyl sulfoxide; at 85℃;
General procedure: p-Chloro-N-alkylbenzenesulfonamides (1-8) (1 equiv.) andaminolactam N-(3-aminopropyl)-2-pyrrolidinone (APP)(1.25 equiv.) or <strong>[24566-95-8]N-(3-aminopropyl)-2-azepanone</strong> (<strong>[24566-95-8]APA</strong>)(1.25 equiv.) were added to a 50 mL round-bottomed flaskand dissolved in dimethylsulfoxide (10 mL) for a nucleophilicaromatic substitution reaction (SNAr). The contents were then stirred in a reflux system for 1-2 h at 85 C.Afterward, the solvent was removed with frozen water andthe product was treated with diluted HCl (5 %) for removalof amino-lactam excess. The crude product was filtered offand recrystallized from 1:1 ethyl ether-petroleum ether (bp60-80 C). All obtained compounds were structurally confirmedby 13C and 1H NMR analyses (see Supplementarymaterial).
4-chloro-3-nitro-N-cyclohexylbenzenesulfonamide[ No CAS ]
4-[N-(3'-aminopropyl)-2-azepanone]-3-nitro-N-cyclohexylbenzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dimethyl sulfoxide; at 85℃;
General procedure: p-Chloro-N-alkylbenzenesulfonamides (1-8) (1 equiv.) andaminolactam N-(3-aminopropyl)-2-pyrrolidinone (APP)(1.25 equiv.) or <strong>[24566-95-8]N-(3-aminopropyl)-2-azepanone</strong> (<strong>[24566-95-8]APA</strong>)(1.25 equiv.) were added to a 50 mL round-bottomed flaskand dissolved in dimethylsulfoxide (10 mL) for a nucleophilicaromatic substitution reaction (SNAr). The contents were then stirred in a reflux system for 1-2 h at 85 C.Afterward, the solvent was removed with frozen water andthe product was treated with diluted HCl (5 %) for removalof amino-lactam excess. The crude product was filtered offand recrystallized from 1:1 ethyl ether-petroleum ether (bp60-80 C). All obtained compounds were structurally confirmedby 13C and 1H NMR analyses (see Supplementarymaterial).
4-chloro-3-nitro-N-4-chlorobenzylbenzenesulfonamide[ No CAS ]
4-[N-(3'-aminopropyl)-2-azepanone]-3-nitro-N-4-chlorobenzylbenzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dimethyl sulfoxide; at 85℃;
General procedure: p-Chloro-N-alkylbenzenesulfonamides (1-8) (1 equiv.) andaminolactam N-(3-aminopropyl)-2-pyrrolidinone (APP)(1.25 equiv.) or <strong>[24566-95-8]N-(3-aminopropyl)-2-azepanone</strong> (<strong>[24566-95-8]APA</strong>)(1.25 equiv.) were added to a 50 mL round-bottomed flaskand dissolved in dimethylsulfoxide (10 mL) for a nucleophilicaromatic substitution reaction (SNAr). The contents were then stirred in a reflux system for 1-2 h at 85 C.Afterward, the solvent was removed with frozen water andthe product was treated with diluted HCl (5 %) for removalof amino-lactam excess. The crude product was filtered offand recrystallized from 1:1 ethyl ether-petroleum ether (bp60-80 C). All obtained compounds were structurally confirmedby 13C and 1H NMR analyses (see Supplementarymaterial).
4-chloro-3-nitro-N-2,4-dichlorobenzylbenzenesulfonamide[ No CAS ]
4-[N-(3'-aminopropyl)-2-azepanone]-3-nitro-N-2,4-dichlorobenzylbenzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dimethyl sulfoxide; at 85℃;
General procedure: p-Chloro-N-alkylbenzenesulfonamides (1-8) (1 equiv.) andaminolactam N-(3-aminopropyl)-2-pyrrolidinone (APP)(1.25 equiv.) or <strong>[24566-95-8]N-(3-aminopropyl)-2-azepanone</strong> (<strong>[24566-95-8]APA</strong>)(1.25 equiv.) were added to a 50 mL round-bottomed flaskand dissolved in dimethylsulfoxide (10 mL) for a nucleophilicaromatic substitution reaction (SNAr). The contents were then stirred in a reflux system for 1-2 h at 85 C.Afterward, the solvent was removed with frozen water andthe product was treated with diluted HCl (5 %) for removalof amino-lactam excess. The crude product was filtered offand recrystallized from 1:1 ethyl ether-petroleum ether (bp60-80 C). All obtained compounds were structurally confirmedby 13C and 1H NMR analyses (see Supplementarymaterial).
4-[N-(3′-aminopropyl)-2-azepanone]-3-nitro-N-butylbenzenesulfonamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dimethyl sulfoxide; at 85℃;
General procedure: p-Chloro-N-alkylbenzenesulfonamides (1-8) (1 equiv.) andaminolactam N-(3-aminopropyl)-2-pyrrolidinone (APP)(1.25 equiv.) or <strong>[24566-95-8]N-(3-aminopropyl)-2-azepanone</strong> (<strong>[24566-95-8]APA</strong>)(1.25 equiv.) were added to a 50 mL round-bottomed flaskand dissolved in dimethylsulfoxide (10 mL) for a nucleophilicaromatic substitution reaction (SNAr). The contents were then stirred in a reflux system for 1-2 h at 85 C.Afterward, the solvent was removed with frozen water andthe product was treated with diluted HCl (5 %) for removalof amino-lactam excess. The crude product was filtered offand recrystallized from 1:1 ethyl ether-petroleum ether (bp60-80 C). All obtained compounds were structurally confirmedby 13C and 1H NMR analyses (see Supplementarymaterial).
2-(4-methyl-1,4-diazepan-1-yl)-N-(3-(2-oxoazepan-1-yl)propyl)-5-oxo-5H-benzo[4,5]thiazolo[3,2-a][1,8]naphthyridine-6-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
With aluminum (III) chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene; In dichloromethane; at 0 - 20℃;
To a 5 L reactor was added ethyl 2-(4-methyl-l,4-diazepan-l-yl)-5-oxo-5i7- benzo[4,5]thiazolo[3,2-a][l,8]naphthyridine-6-carboxylate (50.5 g) and DCM (1100 ml). To the mixture was added DBU (55 ml) and l-(3-Aminopropyl)hexahydro-lH-azepin-2-one (41 g) then cooled to 0-5 C. AlCb (20.3 g) was added slowly while maintaining the temperature at no more than 15 C. The mixture was warmed up to room temperature and stirred overnight. The mixture was added 1000 ml of 2 N NaOH(aq) for extraction. The aqueous layer was extracted with 300 ml of DCM. The combined organic layer was extracted with 1000 ml of HCl(aq) (pH = 1). The organic layer was extracted again with 300 ml of HCl(aq) (pH=l). The combined aqueous layer was added 900 ml of DCM. The mixture was added 30% NaOH(aq) to adjust pH to 14. The aqueous layer was extracted with 300 ml of DCM. The combined organic layer was evaporated to dryness. The residue was added 500 ml of THF for slurry at 40 C and then added 500 ml of n-heptane. The mixture was cooled to room temperature and filtrated. The wet cake was washed with 500 ml of THF/n-heptane = 1/1 (v/v). The wet cake was vacuum dried at 40 C overnight to get Compound 8 (54.5 g; 2-(4-methyl-l,4-diazepan-l- yl)-/V-(3-(2-oxoazepan-l-yl)propyl)-5-oxo-5i7-benzo[4,5]thiazolo[3,2-a][l,8]naphthyridine- 6-carboxamide) in 84% yield with 98.3% purity. MS: m/z 561.242 [M+H]+. MP: 185.2-186.6 C. NMR and 13C NMR in CDCb as shown below.
bis(((2R,3R,3aS,9aR)-3-hydroxy-3a-methyl-6-oxo-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-2-yl)methyl) carbonate[ No CAS ]
((2R,3R,3aS,9aR)-3-hydroxy-3a-methyl-6-oxo-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-2-yl)methyl (3-(2-oxoazepan-1-yl)propyl)carbamate[ No CAS ]