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| CAS No. : | 415913-05-2 | 
| Formula : | C9H8N2O2S | 
| M.W : | 208.24 | 
| SMILES Code : | O=S(C1=C2C=CC=NC2=CC=C1)(N)=O | 
| MDL No. : | MFCD02752662 | 
| InChI Key : | DWHIGANEUNBVPB-UHFFFAOYSA-N | 
| Pubchem ID : | 21876443 | 
| GHS Pictogram: |   | 
| Signal Word: | Warning | 
| Hazard Statements: | H302-H315-H319-H335 | 
| Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501 | 
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 82% | With ammonium hydroxide; In 1,4-dioxane; at 0 - 20℃; | a) An aqueous solution of NH4OH (45 mL of 30% w/v) was added to a cold (05C) solution of quinoline-5-sulfonyl chloride (1 g, 4.4 mmol) in dioxane (35 mL) and the reaction was allowed to proceed overnight at RT. Water was added and extracted twice with EtAcO and twice with DCM. The combined organic fractions were dried and the solvent was evaporated to afford quinoline-5-sulfonamide as a slighly brown solid /750 mg, 82% yield)1 H NMR (400 MHz, Chloroform-d) ? 9.13 - 8.92 (m, 2H), 8.36 (d, J = 7.9 Hz, 2H), 7.80 (t, J = 7.9 Hz, 1 H), 7.61 (dd, J = 8.7, 4.1 Hz, 1 H), 4.95 (s, 2H). | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 42% | With pyridine; dmap; at 20℃; for 6h; | b) Acetic anhydride (1 mL, 10.1 mmol) and DMAP (123 mg, 1 .01 mmol) were added to a suspension of <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (700 mg, 3.36 mmol) in pyridine 2 mL and the reaction was allowed to proceed at RT with stirring for 6 h.HPLC-mass spectra showed complete conversion. EtAcO (150 mL) was added and this solution was washed twice with NH4CI sat (50 mL) and H2O (2 x 50 mL). The organic fraction was dried (Mg2S04) and the solvent was removed in vacuo to afford N-(quinolin-5-ylsulfonyl)acetamide as a slightly yellow solid. (350 mg, 42% yield)1 H NMR (300 MHz, Chloroform-d) ? 9.12 - 8.96 (m, 2H), 8.53 (dd, J = 7.5, 1 .3 Hz, 1 H), 8.43 (dt, J = 8.4, 1 .1 Hz, 1 H), 7.86 (dd, J = 8.5, 7.5 Hz, 1 H), 7.61 (dd, J = 8.8, 4.2 Hz, 1 H), 2.05 (s, 3H). | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 2h; | To a solution of Example 80B (7-cyclobutyl-4-methoxy-2,3-dihydrobenzofuran-3-carboxylic acid) (60 mg, 0.242 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (93 mg, 0.483 mmol) and 4-dimethylaminopyridine (4-dimethylaminopyridine) (32.5 mg, 0.266 mmol) in CH2Cl2 (0.3 mL) was added <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (55.4 mg, 0.266 mmol). The mixture was stirred for 2 hours and was partitioned between ethyl acetate (75 mL) and 1 M aqueous HCl (15 mL). The ethyl acetate layer was washed with brine, dried (MgSO4), filtered, concentrated and chromatographed on silica gel, eluting with a gradient of 25% to 100% [200:1:1 ethyl acetate:HCOOH:H2O] in heptanes to provide the title compound. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm 12.80 (s, 1H), 9.09 (dd, J=1.6, 4.2 Hz, 1H), 9.04 (ddd, J=1.0, 1.5, 8.7 Hz, 1H), 8.39-8.34 (m, 2H), 7.94 (dd, J=7.5, 8.4 Hz, 1H), 7.82 (dd, J=4.2, 8.8 Hz, 1H), 6.96 (d, J=8.4 Hz, 1H), 6.29 (d, J=8.4 Hz, 1H), 4.67-4.60 (m, 1H), 4.29-4.22 (m, 2H), 3.41-3.32 (m, 1H), 3.21 (s, 3H), 2.16-1.95 (m, 4H), 1.92-1.80 (m, 1H), 1.77-1.68 (m, 1H). MS (APCI+) m/z 439 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; | Example 11B (100 mg, 0.35 mmol, 1.0 equivalent), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (132.3 mg, 0.70 mmol, 2.0 equivalents) and 4-dimethylaminopyridine (46.81 mg, 0.38 mmol, 1.1 equivalents) were dissolved in dichloromethane (1 mL). The solution was added to a vial containing 5-quinoline-1-sulfonamide (124.9 mg, 0.060 mmol, 1.2 equivalents) and the mixture was stirred overnight at room temperature. The solvent was removed under N2 and the residue was reconstituted in 1:1 v/v dimethylsulfoxide/methanol, and was purified via preparative reverse phase HPLC/MS method 7 to provide the title compound. 1H NMR (501 MHz, dimethylsulfoxide-d6:D2O=9:1 (v/v)) δ ppm 9.10 (dd, J=4.2, 1.6 Hz, 1H), 9.06 (ddd, J=8.8, 1.6, 0.9 Hz, 1H), 8.39 (dt, J=8.5, 1.1 Hz, 1H), 8.36 (dd, J=7.5, 1.2 Hz, 1H), 7.97 (dd, J=8.5, 7.5 Hz, 1H), 7.87 (dd, J=8.8, 4.2 Hz, 1H), 7.31 (d, J=8.8 Hz, 1H), 6.30 (d, J=8.9 Hz, 1H), 4.11 (dt, J=11.0, 4.0 Hz, 1H), 3.82-3.77 (m, 1H), 3.71-3.63 (m, 1H), 2.96 (s, 3H), 2.14-2.03 (m, 1H), 1.88-1.80 (m, 1H). MS (APCI+) m/z 476.9 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| A solution of Example 81B (5-cyclobutyl-8-methoxyisochroman-1-carboxylic acid) (16 mg, 0.061 mmol) in CH2Cl2 (0.5 mL) was treated with oxalyl chloride (26.7 μl, 0.305 mmol), treated with a catalytic amount of N,N-dimethylformamide, stirred at room temperature for 30 minutes and concentrated to dryness with a stream of nitrogen for 45 minutes. The residue was dissolved in CH2Cl2 (0.5 mL), treated with <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (16.51 mg, 0.079 mmol), treated with triethylamine (17.00 μl, 0.122 mmol), treated with a catalytic amount of 4-dimethylaminopyridine, and stirred at room temperature overnight. The mixture was partitioned between ethyl acetate (75 mL) and 1 M aqueous HCl (15 mL). The ethyl acetate layer was washed with brine, dried (MgSO4), filtered, concentrated and chromatographed on silica gel, eluting with a gradient of 15% to 50% [200:1:1 ethyl acetate:HCOOH:H2O] in heptanes to provide the title compound. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm 12.91 (s, 1H), 9.11-9.05 (m, 2H), 8.38-8.31 (m, 2H), 7.93 (dd, J=7.6, 8.2 Hz, 1H), 7.83 (dd, J=4.2, 8.7 Hz, 1H), 7.03 (d, J=8.5 Hz, 1H), 6.58 (d, J=8.4 Hz, 1H), 5.04 (s, 1H), 3.73-3.66 (m, 1H), 3.52-3.39 (m, 2H), 2.97 (s, 3H), 2.58-2.46 (m, 1H), 2.40 (dt, J=3.7, 16.7 Hz, 1H), 2.24-2.14 (m, 2H), 2.03-1.86 (m, 3H), 1.77-1.67 (m, 1H). MS (ESI+) m/z 453 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; | Into a 4 mL vial was added crude 5-cyclobutyl-8-methoxychroman-4-carboxylic acid (110 mg, 0.419 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (161 mg, 0.839 mmol), and N,N-dimethylpyridin-4-amine (56.4 mg, 0.461 mmol) in dichloromethane (4 mL). Quinoline-5-sulfonamide (96 mg, 0.461 mmol) was added. The reaction was stirred overnight at room temperature. The solvent was removed under a stream of nitrogen, and the residue was reconstituted in dimethyl sulfoxide/CH3OH and purified via preparative reverse phase HPLC method TFA7 to provide the title compound. 1H NMR (400 MHz, DMSO-d6:D2O=9:1 (v/v)) δ ppm 9.19-9.08 (m, 2H), 8.43-8.31 (m, 2H), 7.96 (dd, J=8.4, 7.5 Hz, 1H), 7.90 (dd, J=8.6, 4.4 Hz, 1H), 6.74 (d, J=8.4 Hz, 1H), 6.58 (d, J=8.4 Hz, 1H), 4.10 (dt, J=11.0, 3.4 Hz, 1H), 3.68 (d, J=2.6 Hz, 1H), 3.64 (s, 3H), 3.62-3.49 (m, 1H), 2.44 (p, J=8.7 Hz, 1H), 2.15-1.91 (m, 3H), 1.66 (p, J=9.7 Hz, 1H), 1.44 (p, J=9.5 Hz, 1H), 1.38-1.26 (m, 1H), 1.11-0.93 (m, 1H), 0.93-0.77 (m, 1H). MS (APCI+) m/z 453.0 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (77 mg, 0.40 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (27 mg, 0.22 mmol) in anhydrous dichloromethane (2 mL), 1-(6-cyclobutyl-3-isopropoxy-2-pyridyl)cyclopropanecarboxylic acid (55 mg, 0.20 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (41 mg, 0.20 mmol) was added and the reaction mixture was stirred at reflux for 1 hour. The reaction mixture was treated with water and organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.23 (ddd, J=8.7, 1.7, 0.8 Hz, 1H), 8.90 (dd, J=4.3, 1.7 Hz, 1H), 8.27 (dd, J=7.3, 1.2 Hz, 1H), 8.13 (dt, J=8.5, 1.1 Hz, 1H), 7.78 (dd, J=8.5, 7.3 Hz, 1H), 7.59 (dd, J=8.7, 4.3 Hz, 1H), 7.10 (q, J=8.4 Hz, 2H), 4.31 (hept, J=6.0 Hz, 1H), 3.62-3.49 (m, 1H), 2.32-2.12 (m, 4H), 2.08-1.92 (m, 1H), 1.90-1.76 (m, 1H), 1.52 (q, J=3.8 Hz, 2H), 1.05 (q, J=3.9 Hz, 2H), 0.93 (d, J=6.0 Hz, 6H)+ MS (ESI+) m/z 466 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (103 mg, 0.56 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (38 mg, 0.31 mmol) in anhydrous dichloromethane (2 mL), 1-(6-ethyl-3-isopropoxy-2-pyridyl)cyclopropanecarboxylic acid (70 mg, 0.28 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (58 mg, 0.28 mmol) was added and the reaction mixture was stirred at reflux overnight. The reaction mixture was treated with water and organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.20 (ddd, J=8.7, 1.7, 0.8 Hz, 1H), 8.87 (dd, J=4.3, 1.7 Hz, 1H), 8.25 (dd, J=7.3, 1.2 Hz, 1H), 8.09 (dt, J=8.5, 1.1 Hz, 1H), 7.74 (dd, J=8.5, 7.3 Hz, 1H), 7.57 (dd, J=8.7, 4.3 Hz, 1H), 7.10 (d, J=8.5 Hz, 1H), 6.98 (d, J=8.4 Hz, 1H), 4.29 (hept, J=6.0 Hz, 1H), 2.63 (q, J=7.6 Hz, 2H), 1.52 (q, J=3.8 Hz, 2H), 1.21-1.10 (m, 3H), 1.01 (q, J=3.8 Hz, 2H), 0.92 (d, J=6.0 Hz, 6H)+ MS (ESI+) m/z 440 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 48h; | To a solution of Example 109 I-12B (1-(5-cyclopropyl-2-methoxyphenyl)cyclopropanecarboxylic acid) (15 mg, 0.065 mmol), 33 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (24.76 mg, 0.129 mmol) and 62 <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (14.79 mg, 0.071 mmol) in 51 N,N-dimethylformamide (0.3 mL) was added 34 4-dimethylaminopyridine (8.68 mg, 0.071 mmol). The mixture was stirred for 2 days at ambient temperature. The mixture was treated with additional 4-dimethylaminopyridine (5 mg) and <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (10 mg) and stirred at ambient temperature for 2 hours. The mixture was partitioned between methyl tert-butyl ether (75 mL) and 1 M aqueous HCl (15 mL). The methyl tert-butyl ether layer was washed with 0.2 M aqueous HCl (10 mL), washed with brine, dried (MgSO4), filtered, concentrated and chromatographed on silica gel, eluting with a gradient of 25% to 100% [200:1:1 ethyl acetate:HCOOH:H2O] in heptanes to provide the 113 title compound. 1H NMR (501 MHz, dimethyl sulfoxide-d6) δ ppm 11.56 (s, 1H), 9.04 (dd, J=1.6, 4.1 Hz, 1H), 8.97 (dd, J=1.1, 8.8 Hz, 1H), 8.35-8.29 (m, 2H), 7.93 (t, J=7.9 Hz, 1H), 7.70 (dd, J=4.2, 8.8 Hz, 1H), 6.93 (dd, J=2.3, 8.4 Hz, 1H), 6.84 (d, J=2.3 Hz, 1H), 6.74 (d, J=8.5 Hz, 1H), 3.31 (s, 3H), 1.84 (tt, J=5.1, 8.5 Hz, 1H), 1.21 (q, J=4.2 Hz, 2H), 0.93 (s, 2H), 0.89-0.85 (m, 2H), 0.62-0.58 (m, 2H)+ LC/MS (APCI+) m/z 423 (M+H)+ | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (92 mg, 0.48 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (32 mg, 0.26 mmol) in anhydrous dichloromethane (2 mL), 1-(2,5-diisopropoxy-3-pyridyl)cyclopropanecarboxylic acid (69 mg, 0.24 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (54 mg, 0.24 mmol) was added and the reaction mixture was stirred at reflux overnight. The reaction mixture was treated with water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.16 (ddd, J=8.7, 1.7, 0.9 Hz, 1H), 8.88 (dd, J=4.3, 1.7 Hz, 1H), 8.25 (dd, J=7.3, 1.3 Hz, 1H), 8.13 (dt, J=8.5, 1.1 Hz, 1H), 7.78 (dd, J=8.5, 7.3 Hz, 1H), 7.57 (dd, J=8.7, 4.3 Hz, 1H), 7.53 (d, J=3.0 Hz, 1H), 7.12 (d, J=3.0 Hz, 1H), 4.92-4.78 (m, 1H), 4.41 (hept, J=6.1 Hz, 1H), 1.45 (q, J=3.9 Hz, 2H), 1.26 (d, J=6.1 Hz, 6H), 0.92 (d, J=6.1 Hz, 6H), 0.84 (q, J=3.9 Hz, 2H)+ MS (ESI+) m/z 470 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (96 mg, 0.50 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (33 mg, 0.27 mmol) in anhydrous dichloromethane (2 mL), 1-(2-isobutoxy-5-methoxy-3-pyridyl)cyclopropanecarboxylic acid (63 mg, 0.25 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (52 mg, 0.25 mmol) was added and the reaction mixture was stirred at reflux overnight. The reaction was treated with water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.18 (ddd, J=8.7, 1.7, 0.9 Hz, 1H), 8.90 (dd, J=4.3, 1.7 Hz, 1H), 8.26 (dd, J=7.3, 1.2 Hz, 1H), 8.13 (dt, J=8.5, 1.1 Hz, 1H), 7.78 (dd, J=8.5, 7.3 Hz, 1H), 7.61-7.54 (m, 2H), 7.14 (d, J=3.0 Hz, 1H), 4.85 (h, J=6.1 Hz, 1H), 3.77 (s, 3H), 1.47 (q, J=3.9 Hz, 2H), 0.92 (d, J=6.2 Hz, 6H), 0.85 (q, J=3.9 Hz, 2H)+ MS (ESI+) m/z 442 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (134 mg, 0.70 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (47 mg, 0.38 mmol) in anhydrous dichloromethane (2 mL), 1-(2-isobutoxy-5-methoxy-3-pyridyl)cyclopropanecarboxylic acid (93 mg, 0.35 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (72 mg, 0.35 mmol) was added and the reaction mixture was stirred at reflux overnight. The reaction was treated with water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 8.89-8.82 (m, 2H), 8.22 (d, J=7.3 Hz, 1H), 8.11 (d, J=8.5 Hz, 1H), 7.83-7.75 (m, 1H), 7.57-7.49 (m, 2H), 7.20 (d, J=4.4 Hz, 1H), 3.78 (s, 3H), 3.27 (d, J=6.5 Hz, 2H), 1.37 (d, J=6.2 Hz, 2H), 0.97 (dt, J=13.3, 6.6 Hz, 1H), 0.79-0.75 (m, 2H), 0.48 (d, J=6.8 Hz, 6H)+ MS (ESI+) m/z 456 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (53 mg, 0.28 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (18 mg, 0.15 mmol) in anhydrous dichloromethane (2 mL), 1-(6-isobutoxy-3-isopropoxy-2-pyridyl)cyclopropanecarboxylic acid (41 mg, 0.14 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (29 mg, 0.14 mmol) was added and the reaction mixture was stirred at reflux overnight. The reaction mixture was quenched with aqueous HCl (1N, 280 μL, 0.28 mmol) and water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.23 (ddd, J=8.8, 1.7, 0.9 Hz, 1H), 8.88 (dd, J=4.3, 1.6 Hz, 1H), 8.31 (dd, J=7.3, 1.3 Hz, 1H), 8.12 (dt, J=8.5, 1.1 Hz, 1H), 7.78 (dd, J=8.5, 7.3 Hz, 1H), 7.59 (dd, J=8.7, 4.3 Hz, 1H), 7.14 (d, J=8.8 Hz, 1H), 6.52 (d, J=8.7 Hz, 1H), 4.16 (hept, J=6.1 Hz, 1H), 3.91 (d, J=6.6 Hz, 2H), 2.09-1.95 (m, 1H), 1.42 (q, J=3.8 Hz, 2H), 1.04 (q, J=3.8 Hz, 2H), 1.00 (d, J=6.8 Hz, 6H), 0.86 (d, J=6.0 Hz, 6H)+ MS (ESI+) m/z 484 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (134 mg, 0.70 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (47 mg, 0.38 mmol) in anhydrous dichloromethane (2 mL), 1-[2-(cyclopropylmethoxy)-5-methoxy-3-pyridyl]cyclopropanecarboxylic acid (92 mg, 0.35 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (72 mg, 0.35 mmol) was added and the reaction mixture was stirred at reflux overnight. The reaction mixture was quenched with aqueous HCl (1N, 700 μL, 0.70 mmol) and water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% formic acid/acetonitrile+0.1% formic acid to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.10 (ddd, J=8.7, 1.7, 0.9 Hz, 1H), 8.86 (dd, J=4.3, 1.7 Hz, 1H), 8.28 (dd, J=7.3, 1.2 Hz, 1H), 8.11 (dt, J=8.5, 1.1 Hz, 1H), 7.77 (dd, J=8.5, 7.3 Hz, 1H), 7.58-7.50 (m, 2H), 7.16 (d, J=3.0 Hz, 1H), 3.78 (s, 3H), 3.69 (d, J=6.3 Hz, 2H), 1.41 (q, J=3.9 Hz, 2H), 0.82 (q, J=3.9 Hz, 2H), 0.74-0.62 (m, 1H), 0.27-0.16 (m, 2H), -0.01-0.03 (m, 2H)+ MS (ESI+) m/z 454 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (77 mg, 0.40 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (26 mg, 0.22 mmol) in anhydrous dichloromethane (2 mL), 1-[5-(cyclopropylmethoxy)-2-methoxy-4-pyridyl]cyclopropanecarboxylic acid (53 mg, 0.20) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (42 mg, 0.20 mmol) was added and the reaction mixture was stirred at reflux overnight. The reaction mixture was quenched with aqueous HCl 1N (400 μL, 0.4 mmol) and water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% formic acid/acetonitrile+0.1% formic acid to give the compound with impurities. The residue was purified by flash chromatography on silica gel (10 g ultra Biotage) eluting with a gradient of 0-3% methanol in dichloromethane to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.03-8.96 (m, 2H), 8.47 (dd, J=7.5, 1.2 Hz, 1H), 8.35 (d, J=8.5 Hz, 1H), 7.93 (dd, J=8.5, 7.4 Hz, 1H), 7.67 (dd, J=8.7, 4.4 Hz, 1H), 7.58 (s, 1H), 6.66 (s, 1H), 5.49 (s, 1H), 3.87 (s, 3H), 3.41 (d, J=6.4 Hz, 2H), 1.39 (q, J=4.5 Hz, 2H), 1.06 (q, J=4.5 Hz, 2H), 0.30-0.19 (m, 2H), -0.05-0.02 (m, 2H)+ MS (ESI+) m/z 454 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (115 mg, 0.60 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (40 mg, 0.33 mmol) in anhydrous dichloromethane (2 mL), 1-[5-cyclobutyl-2-(2-methoxyethoxy)-3-pyridyl]cyclopropanecarboxylic acid (87 mg, 0.30 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (62 mg, 0.30 mmol) was added and the reaction mixture was stirred at reflux for 2 hours. The reaction mixture was quenched with aqueous HCl (1N, 600 μL, 0.60 mmol) and water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, chloroform-d) δ ppm 9.10-9.02 (m, 1H), 8.94 (dd, J=4.2, 1.7 Hz, 1H), 8.27-8.17 (m, 2H), 7.80 (d, J=2.3 Hz, 1H), 7.69 (dd, J=8.5, 7.3 Hz, 1H), 7.44 (dd, J=8.7, 4.2 Hz, 1H), 7.25 (d, J=2.4 Hz, 1H), 4.36-4.29 (m, 2H), 3.65-3.58 (m, 2H), 3.44-3.31 (m, 4H), 2.32-2.20 (m, 2H), 2.02-1.93 (m, 3H), 1.88-1.78 (m, 1H), 1.52 (q, J=3.9 Hz, 2H), 0.90 (q, J=3.9 Hz, 2H)+ MS (ESI+) m/z 482 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (96 mg, 0.50 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (33 mg, 0.27 mmol) in anhydrous dichloromethane (2 mL), 1-[2-(cyclopropylmethoxy)-5-methyl-3-pyridyl]cyclopropanecarboxylic acid (62 mg, 0.25 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (52 mg, 0.25 mmol) was added and the reaction mixture was stirred at reflux for 2 hours. The reaction mixture was quenched with aqueous HCl (1N, 500 μL, 0.50 mmol) and water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.11 (ddd, J=8.7, 1.7, 0.9 Hz, 1H), 8.86 (dd, J=4.3, 1.7 Hz, 1H), 8.28 (dd, J=7.4, 1.3 Hz, 1H), 8.11 (dt, J=8.5, 1.1 Hz, 1H), 7.78 (dd, J=8.5, 7.3 Hz, 1H), 7.68 (dd, J=2.4, 0.9 Hz, 1H), 7.54 (dd, J=8.7, 4.3 Hz, 1H), 7.33 (dd, J=2.4, 0.6 Hz, 1H), 3.70 (d, J=6.3 Hz, 2H), 2.20 (t, J=0.7 Hz, 3H), 1.41 (q, J=3.9 Hz, 2H), 0.80 (q, J=3.9 Hz, 2H), 0.74-0.62 (m, 1H), 0.27-0.16 (m, 2H), 0.06--0.04 (m, 2H)+ MS (ESI+) m/z 438 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (88 mg, 0.46 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (30 mg, 0.25 mmol) in anhydrous dichloromethane (2 mL), 1-[5-cyclobutyl-2-(cyclopropylmethoxy)-3-pyridyl]cyclopropanecarboxylic acid (66 mg, 0.23 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (48 mg, 0.23 mmol) was added and the reaction mixture was stirred at reflux for 2 hours. The reaction mixture was quenched with aqueous HCl (1N, 460 μL, 0.46 mmol) and water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, chloroform-d) δ ppm 8.99 (d, J=8.7 Hz, 1H), 8.95 (dd, J=4.2, 1.7 Hz, 1H), 8.26 (ddd, J=16.8, 7.8, 1.2 Hz, 2H), 7.82 (dd, J=2.4, 0.8 Hz, 1H), 7.71 (dd, J=8.5, 7.3 Hz, 1H), 7.43 (dd, J=8.7, 4.2 Hz, 1H), 7.27 (d, J=2.4 Hz, 8H), 3.98 (d, J=6.5 Hz, 2H), 3.39 (p, J=9.0 Hz, 1H), 2.32-2.22 (m, 3H), 2.02-1.94 (m, 2H), 1.84 (dd, J=7.5, 5.4 Hz, 1H), 1.50 (q, J=3.9 Hz, 2H), 1.04-0.94 (m, 1H), 0.94-0.89 (m, 2H), 0.44-0.33 (m, 2H), 0.20 (dt, J=6.1, 4.5 Hz, 2H)+ MS (ESI+) m/z 478 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (118 mg, 0.62 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (41 mg, 0.34 mmol) in anhydrous dichloromethane (2 mL), 1-[5-ethyl-2-(2-methoxyethoxy)-3-pyridyl]cyclopropanecarboxylic acid (82 mg, 0.31 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (64 mg, 0.31 mmol) was added and the reaction mixture was stirred at reflux for 2 hours. The reaction mixture was quenched with aqueous HCl (1N, 620 μL, 0.62 mmol) and water. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 Mm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, chloroform-d) δ ppm 9.09-9.03 (m, 1H), 8.94 (dd, J=4.2, 1.7 Hz, 1H), 8.24 (dd, J=7.3, 1.3 Hz, 1H), 8.21 (d, J=8.4 Hz, 1H), 7.80 (d, J=2.3 Hz, 1H), 7.69 (dd, J=8.5, 7.3 Hz, 1H), 7.44 (dd, J=8.7, 4.2 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), 4.37-4.30 (m, 2H), 3.67-3.60 (m, 2H), 3.38 (s, 3H), 2.48 (q, J=7.6 Hz, 2H), 1.52 (q, J=3.9 Hz, 2H), 1.14 (t, J=7.6 Hz, 3H), 0.90 (q, J=4.0 Hz, 2H)+ MS (ESI+) m/z 456 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; for 1.33333h; | To a solution of Example I-14D (1-(5-isopropoxy-2-methoxyphenyl)cyclopropanecarboxylic acid) (15 mg, 0.060 mmol), 33 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (22.98 mg, 0.120 mmol) and 62 <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (18.72 mg, 0.090 mmol) in 51 N,N-dimethylformamide (0.3 mL) was added 34 4-dimethylaminopyridine (14.64 mg, 0.120 mmol). The mixture was stirred for 80 minutes. The mixture was partitioned between methyl tert-butyl ether (50 mL) and 0.2 M aqueous HCl (15 mL). The methyl tert-butyl ether layer was washed with 0.2 M aqueous HCl (10 mL), washed with brine, dried (MgSO4), filtered, concentrated and chromatographed on silica gel, eluting with a gradient of 25% to 100% [200:1:1 ethyl acetate:HCOOH:H2O] in heptanes to provide the 115 title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 11.62 (bs, 1H), 9.04 (dd, J=1.5, 4.1 Hz, 1H), 8.98 (d, J=8.7 Hz, 1H), 8.37-8.29 (m, 2H), 7.93 (t, J=7.9 Hz, 1H), 7.69 (dd, J=4.2, 8.8 Hz, 1H), 6.80 (dd, J=2.8, 8.9 Hz, 1H), 6.76 (d, J=8.8 Hz, 1H), 6.66 (d, J=2.8 Hz, 1H), 4.47 (hept, J=6.0 Hz, 1H), 3.30 (s, 3H), 1.23 (d, J=6.0 Hz, 6H), 1.22-1.19 (m, 2H), 0.97-0.91 (m, 2H)+ MS (APCI+) m/z 441 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl acetamide; at 20℃; for 16h; | A mixture of 199 1-(2,5-dimethoxyphenyl)cyclopropanecarboxylic acid (23 mg, 0.10 mmol) from Example I-28B, 62 <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (25 mg, 0.12 mmol), EDAC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl, 38 mg, 0.20 mmol) and 34 4-dimethylaminopyridine (13 mg, 0.11 mmol) was diluted with anhydrous N,N-dimethylacetamide (400 μL), stirred at ambient temperature for 16 hours and then purified by reverse-phase HPLC [Waters XBridge C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 10 to 50% gradient of 37 acetonitrile in 0.1% 38 aqueous trifluoroacetic acid] to give the 202 title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 11.60 (bs, 1H), 9.06 (dd, J=4.2, 1.6 Hz, 1H), 9.00-8.96 (m, 1H), 8.35 (dd, J=8.5, 1.2 Hz, 1H), 8.32 (dd, J=7.5, 1.2 Hz, 1H), 7.95 (dd, J=8.5, 7.5 Hz, 1H), 7.71 (dd, J=8.8, 4.2 Hz, 1H), 6.83 (dd, J=8.8, 2.9 Hz, 1H), 6.78 (d, J=8.8 Hz, 1H), 6.71 (d, J=2.9 Hz, 1H), 3.71 (s, 3H), 3.29 (s, 3H), 1.24-1.20 (m, 2H), 0.98-0.94 (m, 2H)+ MS (ESI+) m/z 413 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; for 72h; | To a solution of Example I-31G (1-(5-ethoxy-2-methoxyphenyl)cyclopropanecarboxylic acid) (13 mg, 0.055 mmol), <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (17.19 mg, 0.083 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (21.10 mg, 0.110 mmol) in N,N-dimethylformamide (0.3 mL) was added 4-dimethylaminopyridine (13.44 mg, 0.110 mmol). The mixture was stirred for about 72 hours. The mixture was partitioned between methyl tert-butyl ether (50 mL) and 0.2 M aqueous HCl (15 mL). The methyl tert-butyl ether layer was washed with 0.2 M aqueous HCl (˜10 mL), washed with brine, dried (MgSO4), filtered, concentrated and chromatographed on silica gel, eluting with a gradient of 25% to 100% [200:1:1 ethyl acetate:HCOOH:H2O] in heptanes to provide the title compound. 1H NMR (501 MHz, dimethyl sulfoxide-d6) δ ppm 11.60 (s, 1H), 9.04 (dd, J=1.6, 4.2 Hz, 1H), 8.97 (dt, J=1.2, 8.7 Hz, 1H), 8.36-8.29 (m, 2H), 7.93 (t, J=7.9 Hz, 1H), 7.69 (dd, J=4.2, 8.8 Hz, 1H), 6.81 (dd, J=2.9, 8.9 Hz, 1H), 6.77 (d, J=8.9 Hz, 1H), 6.69 (d, J=2.9 Hz, 1H), 3.96 (q, J=6.9 Hz, 2H), 3.29 (s, 3H), 1.30 (t, J=7.0 Hz, 3H), 1.20 (q, J=4.3 Hz, 2H), 0.96-0.93 (m, 2H)+ LC/MS (APCI+) m/z 427 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 16h; | A solution of Example I-32A (1-(5-cyclobutoxy-2-methoxyphenyl)cyclopropanecarboxylic acid) (8.6 mg, 0.033 mmol), <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (10.24 mg, 0.049 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (12.57 mg, 0.066 mmol) in N,N-dimethylformamide (0.3 mL) was treated with 4-dimethylaminopyridine (8.01 mg, 0.066 mmol) and stirred at ambient temperature for 16 hours. The mixture was diluted with N,N-dimethylformamide and was directly purified by reverse-phase HPLC [Waters XBridge RP18 column, 5 μm, 30*100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in 0.1% trifluoroacetic acid] to afford the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 11.60 (s, 1H), 9.05 (dd, J=1.6, 4.2 Hz, 1H), 8.98 (dt, J=1.1, 8.9 Hz, 1H), 8.35 (d, J=8.5 Hz, 1H), 8.31 (dd, J=1.2, 7.5 Hz, 1H), 7.94 (dd, J=7.6, 8.3 Hz, 1H), 7.70 (dd, J=4.2, 8.8 Hz, 1H), 6.75 (d, J=8.9 Hz, 1H), 6.71 (dd, J=2.9, 8.8 Hz, 1H), 6.61 (d, J=2.8 Hz, 1H), 4.59 (p, J=7.2 Hz, 1H), 3.29 (s, 3H), 2.43-2.34 (m, 2H), 2.06-1.95 (m, 2H), 1.81-1.71 (m, 1H), 1.68-1.56 (m, 1H), 1.21 (q, J=4.3 Hz, 2H), 0.94 (q, J=4.4 Hz, 2H)+ LC/MS (APCI+) m/z 453 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; | Example I-45C 1-(2-ethoxy-6-methoxyphenyl)-N-(quinoline-5-sulfonyl)cyclopropane-1-carboxamide A solution of Example I-45B (1-(2-ethoxy-6-methoxyphenyl)cyclopropanecarboxylic acid) (21 mg, 0.089 mmol), <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (27.8 mg, 0.133 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (34.1 mg, 0.178 mmol) in N,N-dimethylformamide (0.3 mL) was treated with 4-dimethylaminopyridine (21.72 mg, 0.178 mmol) and stirred over night at ambient temperature. The mixture was partitioned between methyl tert-butyl ether (50 mL) and 1 M aqueous HCl (15 mL). The methyl tert-butyl ether layer was washed with 0.2 M aqueous HCl (15 mL), washed with brine, dried (MgSO4), filtered, concentrated and chromatographed on silica gel, eluting with a gradient of 25% to 100% [200:1:1 ethyl acetate:formic acid:H2O] in heptanes to provide the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 11.25 (bs, 1H), 9.05 (dd, J=1.6, 4.1 Hz, 1H), 9.00-8.97 (m, 1H), 8.34 (d, J=8.4 Hz, 1H), 8.29 (dd, J=1.3, 7.5 Hz, 1H), 7.92 (dd, J=7.5, 8.4 Hz, 1H), 7.70 (dd, J=4.1, 8.8 Hz, 1H), 7.21 (t, J=8.3 Hz, 1H), 6.57 (d, J=8.1 Hz, 1H), 6.53 (d, J=8.2 Hz, 1H), 3.79 (q, J=7.0 Hz, 2H), 3.62 (s, 3H), 1.39 (q, J=4.3 Hz, 2H), 0.92 (q, J=4.4 Hz, 2H), 0.87 (t, J=6.9 Hz, 3H)+ LC/MS (APCI+) m/z 427 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 16h; | A solution of Example I-46C (1-(2-(cyclopropylmethoxy)-6-methoxyphenyl)cyclopropanecarboxylic acid) (21.4 mg, 0.082 mmol), <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (25.5 mg, 0.122 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (31.3 mg, 0.163 mmol) in N,N-dimethylformamide (0.3 mL) was treated with 4-dimethylaminopyridine (19.93 mg, 0.163 mmol) and stirred for 16 hours at ambient temperature. The mixture was partitioned between methyl tert-butyl ether (50 mL) and 1 M aqueous HCl (15 mL). The methyl tert-butyl ether layer was washed with 0.2 M aqueous HCl (15 mL), washed with brine, dried (MgSO4), filtered, concentrated, and chromatographed on silica gel, eluting with a gradient of 25% to 100% [200:1:1 ethyl acetate:HCOOH:H2O] in heptanes to provide the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 11.23 (bs, 1H), 9.04 (dd, J=1.6, 4.2 Hz, 1H), 8.99 (dt, J=1.3, 8.7 Hz, 1H), 8.34 (d, J=8.4 Hz, 1H), 8.29 (dd, J=1.2, 7.4 Hz, 1H), 7.92 (dd, J=7.4, 8.5 Hz, 1H), 7.70 (dd, J=4.1, 8.8 Hz, 1H), 7.20 (t, J=8.3 Hz, 1H), 6.57 (d, J=8.2 Hz, 1H), 6.53 (d, J=8.1 Hz, 1H), 3.66 (d, J=6.3 Hz, 2H), 3.61 (s, 3H), 1.41 (q, J=4.4 Hz, 2H), 0.95 (q, J=4.5 Hz, 2H), 0.81-0.72 (m, 1H), 0.26-0.21 (m, 2H), 0.07-0.03 (m, 2H)+ LC/MS (APCI+) m/z 453 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; | A solution of Example I-66C, 1-(2,6-diethoxyphenyl)cyclopropanecarboxylic acid (22.8 mg, 0.091 mmol), <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (37.9 mg, 0.182 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (34.9 mg, 0.182 mmol) and 4-dimethylaminopyridine (22.26 mg, 0.182 mmol) in N,N-dimethylformamide (0.3 mL) was stirred overnight at ambient temperature. The mixture was partitioned between methyl tert-butyl ether (50 mL) and 1 M aqueous HCl (15 mL). The methyl tert-butyl ether layer was washed with 0.2 M aqueous HCl (15 mL), washed with brine, dried (MgSO4), filtered, concentrated and chromatographed on silica gel, eluting with a gradient of 25% to 100% [200:1:1 ethyl acetate:formic acid:H2O] in heptanes to provide the title compound. 1H NMR (501 MHz, dimethyl sulfoxide-d6) δ ppm 11.21 (s, 1H), 9.04 (dd, J=1.6, 4.2 Hz, 1H), 9.00-8.97 (m, 1H), 8.34 (d, J=8.4 Hz, 1H), 8.30 (dd, J=1.3, 7.5 Hz, 1H), 7.92 (dd, J=7.4, 8.4 Hz, 1H), 7.69 (dd, J=4.1, 8.8 Hz, 1H), 7.18 (t, J=8.3 Hz, 1H), 6.52 (d, J=8.3 Hz, 2H), 3.83 (q, J=6.9 Hz, 4H), 1.41 (q, J=4.3 Hz, 2H), 0.98-0.93 (m, 8H)+ LC/MS (APCI+) m/z 441 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, a solution of 1-(5-bromo-2-isopropoxy-3-pyridyl)cyclopropanecarboxylic acid (30 mg, 0.10 mmol) in anhydrous dichloromethane (1 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (43 mg, 0.20 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (15 mg, 0.12 mmol) were added and the mixture was stirred at ambient temperature for 30 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (23 mg, 0.11 mmol) was added and the reaction mixture was stirred at ambient temperature for 2.5 hours. The reaction mixture was treated with water. The organic layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.19-9.12 (m, 1H), 8.88 (dd, J=4.2, 1.7 Hz, 1H), 8.29 (dd, J=7.3, 1.2 Hz, 1H), 8.12 (dt, J=8.5, 1.1 Hz, 1H), 7.95 (d, J=2.6 Hz, 1H), 7.78 (dd, J=8.5, 7.3 Hz, 1H), 7.58 (dd, J=8.8, 4.3 Hz, 1H), 7.55 (d, J=2.6 Hz, 1H), 4.97-4.87 (m, 2H), 1.44 (q, J=4.0 Hz, 2H), 0.91 (d, J=6.2 Hz, 6H), 0.81 (q, J=4.0 Hz, 2H)+ MS (ESI+) m/z 492 (M+2H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]


| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (92 mg, 0.48 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (32 mg, 0.26 mmol) in anhydrous dichloromethane (2 mL), a mixture of 1-[2-isopropyl-6-(trifluoromethyl)-3-pyridyl]cyclopropanecarboxylic acid and 1-[2-propyl-6-(trifluoromethyl)-3-pyridyl]cyclopropanecarboxylic acid (66 mg, 0.24 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (50 mg, 0.24 mmol) was added and the reaction mixture was stirred at reflux for 2 hours. The reaction mixture was quenched with water and the organic layer was separated on phase separator and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% formic acid/acetonitrile+0.1% formic acid to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.05-8.97 (m, 2H), 8.49 (dd, J=7.5, 1.2 Hz, 1H), 8.37 (dt, J=8.5, 1.1 Hz, 1H), 7.95 (dd, J=8.5, 7.4 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.72-7.62 (m, 1H), 7.61-7.51 (m, 1H), 2.41-2.33 (m, 2H), 1.61-1.54 (m, 2H), 1.54-1.40 (m, 2H), 1.18 (q, J=4.4 Hz, 2H), 0.66 (t, J=7.4 Hz, 3H)+ MS (ESI+) m/z 464 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (32 mg, 0.16 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (11 mg, 0.09 mmol) in anhydrous dichloromethane (1 mL), 1-[2-cyclopropyl-6-(trifluoromethyl)-3-pyridyl]cyclopropanecarboxylic acid (22 mg, 0.08 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (17 mg, 0.08 mmol) was added and the reaction mixture was stirred at reflux for 2 hours. The reaction mixture was quenched with water and the organic layer was separated on phase separator and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.10 (ddd, J=8.7, 1.7, 0.9 Hz, 1H), 8.87 (dd, J=4.2, 1.7 Hz, 1H), 8.29 (dd, J=7.3, 1.2 Hz, 1H), 8.13 (dt, J=8.5, 1.1 Hz, 1H), 7.79 (dd, J=8.5, 7.3 Hz, 1H), 7.67-7.60 (m, 1H), 7.51 (dd, J=8.7, 4.3 Hz, 1H), 7.34 (d, J=7.9 Hz, 1H), 5.50 (s, 1H), 2.01 (tt, J=8.1, 4.9 Hz, 1H), 1.58 (d, J=3.4 Hz, 2H), 0.97 (d, J=3.3 Hz, 2H), 0.79 (dd, J=4.8, 3.2 Hz, 2H), 0.50 (dq, J=6.6, 3.2 Hz, 2H)+ MS (ESI+) m/z 462 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(2-cyclopropyl-5-isobutoxy-3-pyridyl)cyclopropanecarboxylic acid (47 mg, 0.20 mmol) in anhydrous dichloromethane (2 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (58 mg, 0.30 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (22 mg, 0.18 mmol) were added and the mixture was stirred at ambient temperature for 5 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (34 mg, 0.165 mmol) was added and the reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was treated with water. The aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 Mm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% formic acid/acetonitrile+0.1% formic acid to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.05 (dt, J=8.8, 1.3 Hz, 1H), 8.96 (dd, J=4.3, 1.6 Hz, 1H), 8.41 (dd, J=7.4, 1.2 Hz, 1H), 8.28 (d, J=8.4 Hz, 1H), 8.09 (s, 1H), 7.96 (d, J=2.8 Hz, 1H), 7.89 (dd, J=8.5, 7.4 Hz, 1H), 7.61 (dd, J=8.8, 4.2 Hz, 1H), 7.44 (s, 1H), 3.85 (d, J=6.4 Hz, 2H), 2.10 (dp, J=13.4, 6.7 Hz, 1H), 1.88 (d, J=5.3 Hz, 1H), 1.57 (d, J=3.1 Hz, 2H), 1.15 (d, J=3.1 Hz, 2H), 1.07 (d, J=6.8 Hz, 6H), 0.76 (dd, J=5.2, 2.5 Hz, 2H), 0.63 (d, J=7.1 Hz, 2H)+ MS (ESI+) m/z 466 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (38 mg, 0.20 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (14 mg, 0.11 mmol) in anhydrous dichloromethane (1 mL), and 1-[2-pyrrolidin-1-yl-6-(trifluoromethyl)-3-pyridyl]cyclopropanecarboxylic acid (30 mg, 0.10 mmol) was added and the mixture was stirred at ambient temperature for 10 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (21 mg, 0.10 mmol) was added and the reaction mixture was stirred at reflux for 1 hour. The reaction mixture was quenched with water and the organic layer was separated on a phase separator and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 Mm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.18 ddd, J=8.7, 1.7, 0.8 Hz, 1H), 8.88 (dd, J=4.3, 1.7 Hz, 1H), 8.28 (dd, J=7.3, 1.2 Hz, 1H), 8.12 (dt, J=8.5, 1.1 Hz, 1H), 7.78 (dd, J=8.5, 7.3 Hz, 1H), 7.57 (dd, J=8.7, 4.3 Hz, 1H), 7.50 (dd, J=7.6, 0.9 Hz, 1H), 6.84 (d, J=7.5 Hz, 1H), 3.33-3.16 (m, 4H), 1.55 (d, J=4.3 Hz, 2H, 1.46-1.30 (m, 4H), 0.97 (d, J=4.5 Hz, 2H)+ MS (ESI+) m/z 491 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(5-isopropoxy-2-methoxy-4-pyridyl)cyclopropanecarboxylic acid (29 mg, 0.115 mmol) in anhydrous dichloromethane (1 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (44 mg, 0.23 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (17 mg, 0.138 mmol) were added and the mixture was stirred at ambient temperature for 5 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (26 mg, 0.126 mmol) was added and the reaction mixture was stirred at ambient temperature for 2.5 hours. The reaction mixture was treated with water and aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.16 (ddd, J=8.8, 1.7, 0.9 Hz, 1H), 8.88 (dd, J=4.3, 1.7 Hz, 1H), 8.26 (dd, J=7.3, 1.3 Hz, 1H), 8.12 (dt, J=8.5, 1.1 Hz, 1H), 7.77 (dd, J=8.5, 7.3 Hz, 1H), 7.57 (dd, J=8.7, 4.3 Hz, 1H), 7.50 (s, 1H), 6.61 (s, 1H), 4.17 (hept, J=6.0 Hz, 1H), 3.82 (s, 3H), 1.43 (q, J=3.9 Hz, 2H), 0.90-0.82 (m, 8H)+ MS (ESI+) m/z 442 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(4-isopropoxy-6-methoxy-3-pyridyl)cyclopropanecarboxylic acid (40 mg, 0.159 mmol) in anhydrous dichloromethane (1 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (61 mg, 0.318 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (23 mg, 0.191 mmol) were added and the mixture was stirred at ambient temperature for 5 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (36 mg, 0.175 mmol) was added and the reaction mixture was stirred at ambient temperature for 2.5 hours. The reaction mixture was treated with water. The aqueous layer was extracted with dichloromethane, and the organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.19 (ddd, J=8.8, 1.7, 0.9 Hz, 1H), 8.88 (dd, J=4.3, 1.7 Hz, 1H), 8.24 (dd, J=7.3, 1.2 Hz, 1H), 8.11 (dt, J=8.5, 1.1 Hz, 1H), 7.77 (dd, J=8.5, 7.3 Hz, 1H), 7.69 (s, 1H), 7.58 (dd, J=8.8, 4.3 Hz, 1H), 6.11 (s, 1H), 4.34 (hept, J=6.0 Hz, 1H), 3.83 (s, 3H), 1.44 (q, J=3.8 Hz, 2H), 0.90 (d, J=6.0 Hz, 6H), 0.80 (q, J=3.8 Hz, 2H)+ MS (ESI+) m/z 442 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Into a vial, to a solution of 1-(5-cyclobutyl-2-isopropoxy-3-pyridyl)cyclopropanecarboxylic acid (65 mg, 0.236 mmol) in anhydrous dimethyl sulfoxide (1 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (90 mg, 0.472 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (29 mg, 0.191 mmol) were added and the mixture was stirred at ambient temperature for 5 minutes. Quinoline-5-sulfonamide (CAS No.415913-05-2) (54 mg, 0.26 mmol) was added and the reaction mixture was stirred at ambient temperature overnight. The mixture was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.14 (ddd, J=8.7, 1.7, 0.8 Hz, 1H), 8.85 (dd, J=4.3, 1.7 Hz, 1H), 8.22 (dd, J=7.3, 1.2 Hz, 1H), 8.09 (dt, J=8.5, 1.1 Hz, 1H), 7.74 (dd, J=8.5, 7.3 Hz, 1H), 7.68 (dd, J=2.4, 0.7 Hz, 1H), 7.53 (dd, J=8.7, 4.3 Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 4.92-4.80 (m, 1H), 3.48-3.35 (m, 1H), 2.31-2.19 (m, 2H), 2.16-1.93 (m, 3H), 1.88-1.79 (m, 1H), 1.43 (q, J=3.9 Hz, 2H), 0.88 (d, J=6.1 Hz, 6H), 0.80 (q, J=3.9 Hz, 2H)+ MS (ESI+) m/z 466 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 1-[5-cyclobutyl-2-(pyrrolidin-1-yl)pyridin-3-yl]-N-(quinoline-5-sulfonyl)cyclopropane-1-carboxamide In a microwave vial, to a solution of 1-(5-cyclobutyl-2-pyrrolidin-1-yl-3-pyridyl)cyclopropanecarboxylic acid (50 mg, 0.174 mmol) in anhydrous N,N-dimethylformamide (1 mL) under N2, <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (40 mg, 0.191 mmol) and N,N-diisopropylethylamine (62 μL, 0.348 mmol) were added and the mixture was stirred at ambient temperature for 5 minutes. Propylphosphonic anhydride solution ˜50% in N,N-dimethylformamide (CAS No.68957-94-8) (179 μL, 0.209 mmol) was added and the reaction mixture was heated at 60 C. for 2 hours. The reaction mixture was cooled down at ambient temperature and the solvent was removed. The mixture was quenched with saturated aqueous NaHCO3 solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.21 (ddd, J=8.8, 1.6, 0.8 Hz, 1H), 8.90 (dd, J=4.3, 1.7 Hz, 1H), 8.28 (dd, J=7.3, 1.2 Hz, 1H), 8.13 (dt, J=8.4, 1.1 Hz, 1H), 7.78 (dd, J=8.5, 7.3 Hz, 1H), 7.63-7.55 (m, 2H), 7.42 (d, J=2.4 Hz, 1H), 3.44-3.31 (m, 1H), 3.21 (d, J=6.3 Hz, 4H), 2.25 (dddd, J=8.6, 6.8, 4.9, 3.5 Hz, 2H), 2.12-1.91 (m, 3H), 1.90-1.77 (m, 1H), 1.57 (q, J=3.6 Hz, 2H), 1.49-1.38 (m, 4H), 0.98 (q, J=3.5 Hz, 2H)+ MS (ESI+) m/z 477 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; dichloromethane;Reflux; | To a solution of 1-(5-cyclopropyl-2-pyrrolidin-1-yl-3-pyridyl)cyclopropanecarboxylic acid (72 mg, 0.264 mmol) in anhydrous dichloromethane (1 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (60 mg, 0.317 mmol), 4-dimethylaminopyridine (CAS No.1122-58-3) (39 mg, 0.317 mmol) and <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (64 mg, 0.29 mmol) were added and the mixture was stirred at reflux overnight. Quinoline-5-sulfonamide (CAS No.415913-05-2) (27 mg, 0.132 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (25 mg, 0.132 mmol) and anhydrous tetrahydrofuran (1 mL) were added and the reaction mixture was stirred and heated at 65 C. overnight. The reaction mixture was cooled down at ambient temperature and the solvent was concentrated. The residue was quenched with saturated aqueous NH4Cl solution and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 Mm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.22 (ddd, J=8.7, 1.7, 0.9 Hz, 1H), 8.89 (dd, J=4.3, 1.7 Hz, 1H), 8.29 (dd, J=7.3, 1.3 Hz, 1H), 8.11 (dt, J=8.5, 1.1 Hz, 1H), 7.77 (dd, J=8.5, 7.3 Hz, 1H), 7.64-7.55 (m, 2H), 7.15 (d, J=2.4 Hz, 1H), 3.17 (d, J=6.3 Hz, 4H), 1.73 (tt, J=8.4, 5.1 Hz, 1H), 1.54 (q, J=3.6 Hz, 2H), 1.48-1.38 (m, 4H), 0.93 (q, J=3.5 Hz, 2H), 0.89-0.78 (m, 2H), 0.57-0.48 (m, 2H)+ MS (ESI+) m/z 463 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 24h;Reflux; | Into a vial, a solution of 1-(5-cyclopropyl-2-isobutoxy-3-pyridyl)cyclopropanecarboxylic acid (60 mg, 0.218 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (50 mg, 0.26 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (32 mg, 0.26 mmol) in anhydrous dichloromethane (2 mL) was added to <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (45 mg, 0.218 mmol). The reaction mixture was stirred at reflux for 24 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.08 (ddd, J=8.7, 1.7, 0.8 Hz, 1H), 8.89 (dd, J=4.3, 1.7 Hz, 1H), 8.25 (dd, J=7.3, 1.2 Hz, 1H), 8.13 (dt, J=8.5, 1.1 Hz, 1H), 7.77 (dd, J=8.5, 7.3 Hz, 1H), 7.69 (dd, J=2.4, 0.5 Hz, 1H), 7.54 (dd, J=8.7, 4.3 Hz, 1H), 7.17 (d, J=2.4 Hz, 1H), 3.55 (d, J=6.6 Hz, 2H), 1.82 (tt, J=8.4, 5.1 Hz, 1H), 1.44 (q, J=3.8 Hz, 2H), 1.35 (hept, J=6.7 Hz, 1H), 0.94-0.86 (m, 2H), 0.82 (q, J=3.9 Hz, 2H), 0.67 (d, J=6.7 Hz, 6H), 0.64-0.58 (m, 2H)+ MS (ESI+) m/z 466 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 24h;Reflux; | Into a vial, a solution of 1-(5-cyclobutyl-2-isobutoxy-3-pyridyl)cyclopropanecarboxylic acid (60 mg, 0.207 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (48 mg, 0.248 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (30 mg, 0.248 mmol) in anhydrous dichloromethane (2 mL) was added to <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (43 mg, 0.207 mmol). The reaction mixture was stirred at reflux for 24 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.09 (dt, J=8.8, 1.2 Hz, 1H), 8.89 (dt, J=4.3, 1.5 Hz, 1H), 8.27 (dt, J=7.3, 1.3 Hz, 1H), 8.13 (dd, J=8.5, 1.2 Hz, 1H), 7.78 (ddd, J=8.5, 7.2, 1.1 Hz, 1H), 7.74-7.69 (m, 1H), 7.54 (ddd, J=8.7, 4.3, 1.1 Hz, 1H), 7.45-7.40 (m, 1H), 3.57 (dd, J=6.5, 1.1 Hz, 2H), 3.48 (p, J=8.7 Hz, 1H), 2.37-2.24 (m, 2H), 2.19-1.96 (m, 3H), 1.93-1.81 (m, 1H), 1.47 (qd, J=3.8, 1.1 Hz, 2H), 1.41-1.29 (m, 2H), 0.84 (qd, J=3.9, 1.0 Hz, 2H), 0.68 (dd, J=6.8, 1.1 Hz, 6H)+ MS (ESI+) m/z 480 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane;Reflux; | Into a vial, a solution of 1-(2-isopropoxy-5-pyrrolidin-1-yl-3-pyridyl)cyclopropanecarboxylic acid (70 mg, 0.24 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (55 mg, 0.288 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (35 mg, 0.288 mmol) in anhydrous dichloromethane (2 mL) was added to <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (50 mg, 0.24 mmol). The reaction mixture was stirred at reflux overnight. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.18 (ddd, J=8.7, 1.7, 0.9 Hz, 1H), 8.88 (dd, J=4.3, 1.7 Hz, 1H), 8.27 (dd, J=7.3, 1.2 Hz, 1H), 8.12 (dt, J=8.5, 1.1 Hz, 1H), 7.78 (dd, J=8.5, 7.3 Hz, 1H), 7.57 (dd, J=8.8, 4.3 Hz, 1H), 7.22 (d, J=3.0 Hz, 1H), 6.92 (d, J=3.0 Hz, 1H), 4.75 (h, J=6.1 Hz, 1H), 3.24-3.16 (m, 4H), 2.03-1.97 (m, 4H), 1.46 (q, J=3.8 Hz, 2H), 0.89 (d, J=6.1 Hz, 6H), 0.85 (q, J=3.9 Hz, 2H)+ MS (ESI+) m/z 481 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane;Reflux; | Into a vial, a solution of 1-(2-isobutoxy-5-pyrrolidin-1-yl-3-pyridyl)cyclopropanecarboxylic acid (44 mg, 0.144 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (363 mg, 0.173 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (21 mg, 0.173 mmol) in anhydrous dichloromethane (2 mL) was added to <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (30 mg, 0.144 mmol). The reaction mixture was stirred at reflux overnight. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 8.97 (dd, J=4.3, 1.5 Hz, 1H), 8.93 (d, J=8.7 Hz, 1H), 8.44 (dd, J=7.4, 1.2 Hz, 1H), 8.31 (d, J=8.5 Hz, 1H), 7.90 (dd, J=8.5, 7.4 Hz, 1H), 7.61 (dd, J=8.7, 4.3 Hz, 1H), 7.32 (d, J=2.7 Hz, 1H), 6.96 (d, J=2.9 Hz, 1H), 3.41 (d, J=6.6 Hz, 2H), 3.24 (h, J=3.6 Hz, 4H), 2.08-1.95 (m, 4H), 1.40 (q, J=4.3 Hz, 2H), 1.18-1.08 (m, 1H), 1.01 (q, J=3.6, 2.9 Hz, 2H), 0.61 (d, J=6.7 Hz, 6H)+ MS (ESI+) m/z 495 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane;Reflux; | Into a vial, a solution of 1-[5-(dimethylamino)-2-isopropoxy-3-pyridyl]cyclopropanecarboxylic acid (41 mg, 0.155 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (36 mg, 0.186 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (23 mg, 0.186 mmol) in anhydrous dichloromethane (2 mL) was added to <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (32 mg, 0.155 mmol). The reaction mixture was stirred at reflux overnight. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.17 (ddd, J=8.7, 1.7, 0.8 Hz, 1H), 8.87 (dd, J=4.3, 1.7 Hz, 1H), 8.25 (dd, J=7.3, 1.2 Hz, 1H), 8.11 (dt, J=8.5, 1.1 Hz, 1H), 7.77 (dd, J=8.5, 7.3 Hz, 1H), 7.57 (dd, J=8.7, 4.3 Hz, 1H), 7.42 (d, J=3.1 Hz, 1H), 7.14 (d, J=3.0 Hz, 1H), 4.79 (h, J=6.1 Hz, 1H), 2.81 (s, 6H), 1.46 (q, J=3.8 Hz, 2H), 0.89 (d, J=6.1 Hz, 6H), 0.84 (q, J=3.9 Hz, 2H)+ MS (ESI+) m/z 455 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 2h;Reflux; | To a solution of 1-(2-isopropoxy-6-methyl-3-pyridyl)cyclopropanecarboxylic acid (80 mg, 0.34 mmol) in anhydrous dichloromethane (3 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (130 mg, 0.68 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (42 mg, 0.34 mmol) were added, followed by <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (64 mg, 0.306 mmol). The reaction mixture was stirred at reflux for 2 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution. The organic layer was separated on a phase separator and was concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, chloroform-d) δ ppm 8.97 (dd, J=4.2, 1.6 Hz, 1H), 8.81 (ddd, J=8.7, 1.6, 0.9 Hz, 1H), 8.47 (dd, J=7.5, 1.3 Hz, 1H), 8.35 (d, J=8.5 Hz, 1H), 7.81 (t, J=8.0 Hz, 1H), 7.45 (dd, J=8.8, 4.2 Hz, 1H), 7.25 (d, J=7.3 Hz, 1H), 6.64-6.57 (m, 1H), 5.38 (p, J=6.1 Hz, 1H), 2.41 (s, 3H), 1.43 (q, J=4.3 Hz, 2H), 1.31-1.24 (m, 7H), 0.90 (q, J=4.3 Hz, 2H)+ MS (ESI+) m/z 426 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 3h;Reflux; | 1-{5-(azetidin-1-yl)-2-[(propan-2-yl)oxy]pyridin-3-yl}-N-(quinoline-5-sulfonyl)cyclopropane-1-carboxamide Into a vial, a solution of 1-[5-(azetidin-1-yl)-2-isopropoxy-3-pyridyl]cyclopropanecarboxylic acid (60 mg, 0.217 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (50 mg, 0.26 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (32 mg, 0.26 mmol) in anhydrous dichloromethane (2 mL) was added on <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (45 mg, 0.217 mmol). The reaction mixture was stirred at reflux for 3 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound with N,N-dimethylaminopyridine. The compound was dissolved in ethyl acetate and washed with saturated aqueous NH4Cl solution (3 times), dried over Na2SO4, filtered and concentrated to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.06 (ddd, J=8.8, 1.6, 0.9 Hz, 1H), 8.99 (dd, J=4.3, 1.6 Hz, 1H), 8.47 (dd, J=7.5, 1.2 Hz, 1H), 8.34 (dt, J=8.5, 1.1 Hz, 1H), 7.93 (dd, J=8.5, 7.4 Hz, 1H), 7.66 (dd, J=8.8, 4.3 Hz, 1H), 7.31 (d, J=2.9 Hz, 1H), 6.80 (d, J=2.9 Hz, 1H), 4.92 ((h, J=6.1 Hz, 1H), 3.86 (t, J=7.2 Hz, 4H), 2.45-2.34 (m, 2H), 1.39-1.31 (m, 2H), 1.04-0.96 (m, 8H)+ MS (ESI+) m/z 467 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 3.5h;Reflux; | Into a vial, a solution of 1-[5-cyclobutyl-2-(4-isopropoxy-1-piperidyl)-3-pyridyl]cyclopropanecarboxylic acid (60 mg, 0.18 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (42 mg, 0.22 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (27 mg, 0.22 mmol) in anhydrous dichloromethane (2 mL) was added to <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (35 mg, 0.18 mmol). The reaction mixture was stirred at reflux for 3.5 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% diethylamine/acetonitrile+0.1% diethylamine to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.19 (ddd, J=8.7, 1.6, 0.8 Hz, 1H), 8.88 (dd, J=4.3, 1.7 Hz, 1H), 8.27 (dd, J=7.3, 1.2 Hz, 1H), 8.12 (dt, J=8.5, 1.1 Hz, 1H), 7.83-7.74 (m, 2H), 7.57 (dd, J=8.7, 4.2 Hz, 1H), 7.48 (dd, J=2.4, 0.6 Hz, 1H), 3.68 (hept, J=6.1 Hz, 1H), 3.50-3.38 (m, 1H), 3.35 (dt, J=8.8, 4.2 Hz, 1H), 3.30-3.22 (m, 2H), 2.62 (ddd, J=12.9, 10.1, 2.7 Hz, 2H), 2.34-2.21 (m, 2H), 2.14-1.94 (m, 3H), 1.91-1.79 (m, 1H), 1.56-1.45 (m, 4H), 1.38-1.27 (m, 2H), 1.13 (d, J=6.1 Hz, 6H), 0.96 (q, J=3.8 Hz, 2H)+ MS (ESI+) m/z 549 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 3.5h;Reflux; | Into a vial, a solution of 1-(5-cyclobutyl-2-ethoxy-3-pyridyl)cyclopropanecarboxylic acid (60 mg, 0.23 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (53 mg, 0.276 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (34 mg, 0.276 mmol) in anhydrous dichloromethane (2 mL) was added to <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (48 mg, 0.23 mmol). The reaction mixture was stirred at reflux for 3.5 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% formic acid/acetonitrile+0.1% formic acid to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.02-8.93 (m, 2H), 8.46 (dd, J=7.5, 1.3 Hz, 1H), 8.34 (dt, J=8.5, 1.1 Hz, 1H), 7.93 (dd, J=8.5, 7.4 Hz, 1H), 7.88 (dd, J=2.4, 0.7 Hz, 1H), 7.63 (dd, J=8.7, 4.3 Hz, 1H), 7.46 (d, J=2.4 Hz, 1H), 3.85 (q, J=7.0 Hz, 2H), 3.52 (p, J=9.3, 8.8 Hz, 1H), 2.40-2.27 (m, 2H), 2.24-2.10 (m, 2H), 2.10-1.98 (m, 1H), 1.95-1.83 (m, 1H), 1.41-1.35 (m, 2H), 1.01 (q, J=4.4 Hz, 2H), 0.80 (t, J=7.0 Hz, 3H)+ MS (ESI+) m/z 452 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; for 3.5h;Reflux; | Into a vial, a solution of 1-(2-ethoxy-5-ethyl-3-pyridyl)cyclopropanecarboxylic acid (60 mg, 0.255 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (59 mg, 0.306 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (37 mg, 0.306 mmol) in anhydrous dichloromethane (2 mL) was added to <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (53 mg, 0.255 mmol). The reaction mixture was stirred at reflux for 3.5 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% formic acid/acetonitrile+0.1% formic acid to give the title compound. 1H NMR (400 MHz, methanol-d4) δ ppm 9.02-8.93 (m, 2H), 8.47 (dd, J=7.5, 1.2 Hz, 1H), 8.34 (dt, J=8.5, 1.1 Hz, 1H), 7.93 (dd, J=8.5, 7.4 Hz, 1H), 7.89-7.84 (m, 1H), 7.63 (dd, J=8.8, 4.3 Hz, 1H), 7.42 (d, J=2.4 Hz, 1H), 3.85 (q, J=7.0 Hz, 2H), 2.59 (q, J=7.6 Hz, 2H), 1.41-1.32 (m, 2H), 1.23 (t, J=7.6 Hz, 3H), 1.04-0.97 (m, 2H), 0.81 (t, J=7.1 Hz, 3H)+ MS (ESI+) m/z 426 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; | To a solution of 1-[5-cyclobutyl-2-[4-(methoxymethyl)-1-piperidyl]-3-pyridyl]cyclopropanecarboxylic acid (118 mg, 0.179 mmol) in anhydrous dichloromethane (3 mL), N,N-diisopropylethylamine (125 μL, 0.716 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS No.25952-53-8) (73 mg, 0.358 mmol) and 4-dimethylaminopyridine (CAS No.1122-58-3) (23 mg, 0.179 mmol) were added, followed by <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (CAS No.415913-05-2) (36 mg, 0.16 mmol). The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was quenched with saturated aqueous NH4Cl solution, and the organic layer was separated on phase separator and concentrated. The crude material was purified by reverse-phase HPLC Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 50 mL/minute, H2O+0.1% formic acid/acetonitrile+0.1% formic acid to give the title compound. 1H NMR (400 MHz, chloroform-d) δ ppm 8.96 (dd, J=4.2, 1.6 Hz, 1H), 8.86 (dt, J=8.8, 1.2 Hz, 1H), 8.50 (dd, J=7.5, 1.2 Hz, 1H), 8.37 (dt, J=8.5, 1.1 Hz, 1H), 8.21 (d, J=2.3 Hz, 1H), 8.11 (s, 1H), 7.83 (dd, J=8.5, 7.5 Hz, 1H), 7.41 (dd, J=8.8, 4.2 Hz, 1H), 7.32 (d, J=2.3 Hz, 1H), 3.48 (dq, J=10.7, 7.4, 5.2 Hz, 3H), 3.36 (s, 3H), 3.25 (d, J=6.0 Hz, 2H), 2.94 (td, J=12.5, 2.3 Hz, 2H), 2.34 (dddd, J=9.9, 7.1, 5.1, 2.9 Hz, 2H), 2.13-2.01 (m, 3H), 1.95-1.83 (m, 1H), 1.81-1.71 (m, 3H), 1.56 (q, J=4.3 Hz, 2H), 1.53-1.38 (m, 2H), 1.12 (q, J=4.3 Hz, 2H)+ MS (ESI+) m/z 535 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 20℃; | In a 4 mL vial was added Example I-30C (64 mg, 0.233 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (89 mg, 0.467 mmol), and N,N-dimethylpyridin-4-amine (31.4 mg, 0.257 mmol) in dichloromethane (1 mL). Quinoline-5-sulfonamide (53.5 mg, 0.257 mmol) was added and the reaction was stirred overnight at ambient temperature. The solvent was removed under a stream of nitrogen and the residue was dissolved in methanol. The sample was purified via preparative reverse phase HPLC/MS method trifluoroacetic acid1, and subsequently repurified using method AA3 to afford the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6:D2O=9:1 (v/v)) δ ppm 9.03 (dd, J=8.7, 1.7 Hz, 1H), 8.90 (dd, J=4.2, 1.7 Hz, 1H), 8.24-8.16 (m, 1H), 8.07 (s, 1H), 8.05 (s, 1H), 7.75 (t, J=7.9 Hz, 1H), 7.52 (dd, J=8.7, 4.2 Hz, 1H), 7.46 (d, J=2.5 Hz, 1H), 2.77 (s, 6H), 1.35-1.30 (m, 2H), 0.79-0.72 (m, 2H)+ MS (APCI) m/z 464.9 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 16h; | Quinoline-5-sulfonamide (24.9 mg, 0.10 mmol, 1.2 eq) was weighed into a 4 mL vial and dichloromethane (0.2 mL) was added. 1-(5-(tert-Butyl)-2-methoxyphenyl)cyclopropanecarboxylic acid (24.8 mg, 0.12 mmol, 1.0 eq) from Example I-34A was mixed with a solution of 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (38.0 mg, 0.2 mmol, 2.0 eq) and 4-dimethylaminopyridine (13.4 mg, 0.11 mmol, 1.1 eq) in dichloromethane (0.5 mL). The stock solution was combined with the sulfonamide and the mixture was stirred for 16 hours at ambient temperature. The solvent was removed under a stream of nitrogen. The residue was dissolved in 1:1 dimethyl sulfoxide/methanol and purified via preparative reverse phase HPLC/MS method trifluoroacetic acid7 to provide the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 9.06 (dd, J=4.2, 1.6 Hz, 1H), 9.01-8.94 (m, 1H), 8.36 (dt, J=8.4, 1.1 Hz, 1H), 8.32 (dd, J=7.5, 1.2 Hz, 1H), 7.96 (dd, J=8.5, 7.5 Hz, 1H), 7.73 (dd, J=8.8, 4.2 Hz, 1H), 7.26 (dd, J=8.6, 2.5 Hz, 1H), 7.08 (d, J=2.5 Hz, 1H), 6.78 (d, J=8.6 Hz, 1H), 3.31 (s, 3H), 1.28 (q, J=4.4 Hz, 2H), 1.23 (s, 9H), 0.97 (q, J=4.6 Hz, 2H)+ MS (APCI) m/z 439.1 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 16h; | Example I-38C 1-[5-(bicyclo[1.1.1]pentan-1-yl)-2-methoxyphenyl]-N-(quinoline-5-sulfonyl)cyclopropane-1-carboxamide Quinoline-5-sulfonamide (24.9 mg, 0.12 mmol, 1.2 eq) was weighed into 4 mL vials and dichloromethane (0.2 mL) was added. 1-(5-(Bicyclo[1.1.1]pentan-1-yl)-2-methoxyphenyl)cyclopropanecarboxylic acid (25.8 mg, 0.12 mmol, 1.0 eq) from Example I-38B was mixed with a solution of 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (38.0 mg, 0.2 mmol, 2.0 eq) and DMAP (4-dimethylaminopyridine, 13.4 mg, 0.11 mmol, 1.1 eq) in dichloromethane (0.5 mL). The stock solution was combined with the sulfonamide and the mixture was stirred for 16 hours at ambient temperature. The solvent was removed under a stream of nitrogen. The residue was dissolved in dimethyl sulfoxide/methanol and purified via preparative reverse phase HPLC/MS method trifluoroacetic acid7 to afford the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 9.05 (dd, J=4.2, 1.6 Hz, 1H), 8.97 (dt, J=8.9, 1.2 Hz, 1H), 8.39-8.28 (m, 2H), 7.95 (dd, J=8.4, 7.5 Hz, 1H), 7.73 (dd, J=8.8, 4.2 Hz, 1H), 7.08 (dd, J=8.3, 2.1 Hz, 1H), 6.91 (d, J=2.1 Hz, 1H), 6.79 (d, J=8.4 Hz, 1H), 3.30 (s, 3H), 2.49 (s, 1H), 1.99 (s, 6H), 1.25 (q, J=4.4 Hz, 2H), 0.95 (q, J=4.5 Hz, 2H)+ MS (APCI) m/z 449.0 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; In N,N-dimethyl acetamide; at 20℃; for 16h; | A mixture of 1-(2,6-dimethoxy-3-methylphenyl)cyclopropanecarboxylic acid (24 mg, 0.10 mmol) from Example I-40D, <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (25 mg, 0.12 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (38 mg, 0.20 mmol) and 4-dimethylaminopyridine (14 mg, 0.11 mmol) in anhydrous N,N-dimethylacetamide (600 μL) was stirred at ambient temperature for 16 hours. The mixture was purified by reverse-phase HPLC [Waters XBridge C18 5 μm OBD column, 30*100 mm, flow rate 40 mL/minute, 10 to 60% gradient of acetonitrile in 0.1% aqueous trifluoroacetic acid] to give the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 11.56 (bs, 1H), 9.08-9.03 (m, 2H), 8.36-8.31 (m, 2H), 7.94 (dd, J=8.4, 7.5 Hz, 1H), 7.74 (dd, J=8.6, 4.4 Hz, 1H), 7.11-7.07 (m, 1H), 6.64 (d, J=8.4 Hz, 1H), 3.54 (s, 3H), 3.30 (s, 3H), 2.08 (s, 3H), 1.50-1.45 (m, 2H), 1.06-1.01 (m, 2H)+ MS (ESI) m/z 427 (M+H)+. | 
 [ 415913-05-2 ]
                                                    
                                                    [ 415913-05-2 ]

| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; | To a solution of 1-(2-methoxy-5-methylphenyl)cyclopropanecarboxylic acid from Example I-44B (0.100 g, 0.485 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.186 g, 0.970 mmol) and N,N-dimethylpyridin-4-amine (0.065 g, 0.533 mmol) in anhydrous dichloromethane (1 mL) was added <strong>[415913-05-2]quinoline-5-sulfonamide</strong> (0.101 g, 0.485 mmol). After 5 hours, the reaction was quenched with 3.5 mL of aqueous 1 N HCl and the organic layer was concentrated in vacuo. The residue was purified via chromatography on a 24 g silica gel cartridge, eluting with ethyl acetate in heptane at a 0-50% gradient over a period of 10 minutes. The crude material was triturated with methanol and filtered to provide the title compound. 1H NMR (501 MHz, dimethyl sulfoxide-d6) δ ppm 11.55 (s, 1H), 9.05 (dd, J=4.2, 1.6 Hz, 1H), 8.98 (dd, J=8.7, 1.1 Hz, 1H), 8.34 (d, J=8.5 Hz, 1H), 8.30 (d, J=7.4 Hz, 1H), 7.93 (t, J=7.9 Hz, 1H), 7.70 (dd, J=8.8, 4.2 Hz, 1H), 7.10-7.03 (m, 1H), 6.94 (d, J=2.2 Hz, 1H), 6.76 (d, J=8.3 Hz, 1H), 3.33 (s, 3H), 2.23 (s, 3H), 1.22 (q, J=4.3 Hz, 2H), 0.93 (q, J=4.4 Hz, 2H)+ MS (APCI+) m/z 397 (M+H)+. |