4-BROMO-N-METHOXY-N-METHYLBENZAMIDE

To a solution of 4-bromobenzoic acid, 5 g (586-76-5, 24.87 minol) in N, N-dimethylformamide, 30 mL, was added triethylamine, 13.9 mL (99.49 minol), N, O-dimethylhydroxylamine hydrochloride, 3.64 g (37.31 minol), 1-hydroxy-7-azabenzotriazole, 5.08 g (37.31 minol) and 1-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 9.54 g (49.75 minol). The reaction was stirred at room temperature for 18 hours. The reaction mixture was diluted with saturatedsolution of sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layers were washed with a saturated solution of sodium hydrogen carbonate, brine dried over solid sodium sulfate, filtered and concentrated under vacuum to give Intermediate 84, 5.6 g (92percent) as a colourless solid.1H NMR (400 MHz, CDCI3): 6 [ppm] = 3.34 (s, 3H), 3.52 (s, 3H), 7.50-7.65 (m, 4H).U PLC-MS (Method 3): R = 0.71 min., 93percent. MS (ESIpos): mz = [M÷H] 244, 246.A solution of 4-bromobenzoic acid (1.0 mg, 5.0 mmol), N, O-dimethylhydroxylamine hydrochloride (536 mg, 5.5 mmol), EDC·HCl (1.05 g, 5.5 mmol), and NEtGeneral procedure: To a solution of 3-cyanobenzoic acid 8a (3.0 g, 19.7 mmol) in DMF was added N, O-dimethylhydroxylamine hydrochloride (2.0 g, 20.7 mmol), EtA solution of 4-bromobenzoyl chloride (4.67 g, 21.3 mmol), diisopropylethylamine (3.78 mL, 46.8 mmol), and NExample 8 Example 10 1-methyl-5-[4-(thien-2-ylcarbonyl)phenyl]-1H-pyrrole-2-carbonitrile To a stirred solution of 4-bromobenzoyl chloride (20.0 g, 91.1 mmol) in dichloromethane (300 mL) at -78° C. was added triethylamine (28.0 mL, 200.0 mmol), and O, N-dimethylhydroxylamine hydrochloride (9.33 g, 95.6 mmol). The resulting solution was allowed to warm to room temperature, stirred for 1.5 hours, and then concentrated. The residue was triturated in acetone and the resulting solid was dissolved in ethyl acetate washed with water and brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated to give 4-bromo-N-methoxy-N-methylbenzamide (18.6 g, 84percent). To a solution of 4-bromo-N-methoxy-N-methylbenzamide (3.0 g, 12.29 mmol) in THF (30 mL) at 0° C. under nitrogen was added 2-thienyllithium (1.0 M in THF, 15 mL, 15 mmol) slowly over 10 minutes. The solution was stirred at 0° C. for 1 hour, poured into a saturated aqueous ammonium chloride solution (150 mL), and extracted several times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The residue was triturated with ether to give (4-bromophenyl)(thien-2-yl)methanone as a brown solid (1.1 g, 34percent). MS (ES) m/z 266.9. The title compound was prepared from (4-bromophenyl)(thien-2-yl)methanone and 1-methyl-2-cyanopyrrole according to the coupling procedure as described in example 1. MS (ES) m/z 293.1; HRMS: calcd for CPyridine (4.40 mL, 54.2 mmol) was added dropwise to N, O-DIMETHYLHYDROXYLAMINE hydrochloride (3.44 g, 35.2 mmol) dissolved in CH2CI2 (100 mL) at RT. The reaction mixture was stirred for 30 min, and 4-BROMOBENZOYL chloride (5.95 g, 27.1 mmol) dissolved in CH2CI2 (50 mL) was added dropwise. The mixture was stirred for 24 h and the volatiles were removed under reduced pressure. Water (200 mL) was added and the mixture was extracted with EtOAc (3 x 200 mL). The combined extracts were washed successively with 5percent aqueous HCI (200 mL), 5percent aqueous NAHC03 (200 mL), water (200 mL), and brine (200 mL). The mixture was dried over MgS04 and concentrated to afford 6.35 G (74percent) of 80 as a colorless oil which was used without further PURIFICATION. H NMR (400 MHz, CDCI3) : 8 3.35 (s, 3H), 3.53 (s, 3H), 7.54 (d, J = 8. 6 HZ, 2H), 7.58 (d, J=8. 6HZ, 2H).

Molecular Weight:244.08
XLogP3:2.1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:242.98949
Monoisotopic Mass:242.98949
Topological Polar Surface Area:29.5
Heavy Atom Count:13
Complexity:179
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes