2-chloro-N-methylaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Chloro-3-(4-chloro-3-(trifluoromethyl)phenylsulfonamido)picolinic acid (50 mg, 0.12 mmol), (2-chloro-phenyl)-methyl-amine (50 mg, 0.36 mmol), BOP (69 mg, 0.36 mmol), DIEA (130 μL, 0.72 mmol) were reacted according to the procedure D to provide the title compound. HPLC purification (20→90% gradient of MeCN-water) provided 5-chloro-3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridine-2-carboxylic acid (2-chloro-phenyl)-methyl-amide: MS m/z: (M+H) 537.4.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-chloro-N-methylaniline (4.96 mmol, 1.1 eq., 702 mg) and pyridine (5.86 mmol, 464 mg) in 20 mL of methylene chloride was added 3-nitrobenzenesulfonyl chloride (4.51 mmol, 1.0 g) in one portion. The reaction mixture was stirred 16 hr and diluted with methylene chloride and water. The aqueous layer was separated and extracted once with methylene chloride. The combined organic layers were extracted once with a saturated solution of aqueous sodium carbonate, once with water, and then dried over sodium sulfate. The crude product was purified using flash chromatography (10-60% ethyl acetate/hexane) to give N-(2-chlorophenyl)-N-methyl-(3-nitrophenyl)sulfonamide which solidifies on standing. 1H NMR (300 MHz) 3.29 (s, 3H), 7.25-7.45 (m, 4H), 7.71 (t, J=7.82 Hz, 1H), 8.06 (d, J=7.82 Hz, 1H), 8.40-8.50 (m, 1H), 8.60-8.65 (m, 1H). MS (ESI): m/e 327.13, 329.13 (M+1). The aqueous layer was separated extracted once with methylene chloride The combined organic layers were extracted once with a saturated solution of aqueous sodium carbonate, once with water dried over sodium sulfate The crude product was purified

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methyl-4H-thieno[3,2-c]chromene-2-carboxylic acid was converted to the acid chloride as in Example 3, then treated with N-methyl-2-chloroaniline (1.5 equiv), and triethylamine (5 equiv) in dichloromethane and N,N-dimethyl-4-aminopyridine (0.2 equiv) at 24° C. After about 24 hr, the reaction mixture was diluted with dichloromethane, and the resulting solution was washed with saturated aqueous sodium bicarbonate. The collected organic was dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (5:2 hexanes/ethylacetate) provided 168bp. 1H (500 MHz, CDCl3) δ 7.53 (d, J=7.7 Hz, 1H), 7.35-7.41 (m, 3H), 6.97 (s, 1H), 6.94 (d, J=8.2 Hz, 1H), 6.76 (d, J=8.2 Hz, 1H), 6.56 (s, 1H), 5.00 (s, 2H), 3.39 (s, 3H), 2.26 (s, 3H). LCMS (ESI) m/z: 370.1 the resulting solution was washed with saturated aqueous sodium bicarbonate The collected organic was dried over anhydrous sodium sulfate filtered concentrated Purification by flash column chromatography (5:2 hexanes/ethylacetate) provided 168bp

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a reaction vial charged with 8-fluoro-4H-thieno[3,2-c]chromene-2-carbonyl chloride (0.05 g, 0.2 mmol) and 2-chloro-N-methylaniline (0.034 g, 0.24 mmol) was added a catalytic amount of DMAP. Pyridine in methylene chloride (1.2 M, 0.66 mL) was added and the reaction was stirred at room temperature with LC/MS monitor. The reaction was complete in a couple hours. After aqueous work up, the reaction was concentrated in vacuo, taken into DMF at 100 mg/ml and purified by preparative RP-HPLC to give 165bp. Yield=28% of theoretical. MS: (ESI+)=374.8 To a reaction After aqueous work up, the reaction was concentrated in vacuo purified by preparative RP-HPLC to give 165bp

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a reaction vial charged with 8-fluoro-4H-thieno[3,2-c]chromene-2-carbonyl chloride (0.05 g, 0.2 mmol) and 2-chloro-N-methylaniline (0.034 g, 0.24 mmol) was added a catalytic amount of DMAP. Pyridine in methylene chloride (1.2 M, 0.66 mL) was added and the reaction was stirred at room temperature with LC/MS monitor. The reaction was complete in a couple hours. After aqueous work up, the reaction was concentrated in vacuo, taken into DMF at 100 mg/ml and purified by preparative RP-HPLC to give 165bp. Yield=28% of theoretical. MS: (ESI+)=374.8 To a reaction After aqueous work up, the reaction was concentrated in vacuo purified by preparative RP-HPLC to give 165bp

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure of Example 70 and General Procedure B, 142bp was prepared from 6,8-difluoro-4H-thieno[3,2-c]chromene-2-carboxylic acid and 2-chloro-N-methylaniline. MS: (ESI+)=392.1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure of Example 70 and General Procedure B, 142bp was prepared from 6,8-difluoro-4H-thieno[3,2-c]chromene-2-carboxylic acid and 2-chloro-N-methylaniline. MS: (ESI+)=392.1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-chloro-N-methylaniline (32.10 uL, 0.2750 mmol) in 1.2 M of Pyridine in methylene chloride (0.8333 mL) was added a pinch of DMAP, followed by the addition of 4,4-dimethyl-4H-thieno[3,2-c]chromene-2-carbonyl chloride (70.2 mg, 0.250 mmol). The reaction was stirred at room temperature under N2 with LC/MS monitor. The crude product was purified on silica to give 30 mg 141bp. Yield=31% of theoretical. MS: (ESI+)=385 The crude product was purified on silica to give 30 mg 141bp