3-BROMO-7-CHLOROIMIDAZO [1,2-A]PYRIDINE

Methyl 3-(l-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxylate (0.150 mg, 0.454 mmol) was dissolved in THF (5 mL) and cooled to -20 C. Following, trimethyl borate (0.103 mL, 0.908 mmol) was added. LDA (0.908 mL, 1.362 mmol) was added to the reaction dropwise over the course of 10 minutes. After about 30 minutes, all starting material was consumed, and the boronic acid was generated. In a separate reaction vessel, lb (0.454 mmol) was dissolved in 7:3 THFAVater and degassed with argon. Sodium carbonate (0.193 g, 1.816 mmol) and Pd2(dppf)Ci2 (8.30 mg, 0.011 mmol) was added, and the reaction was heated to 65 C. The boronic acid was added dropwise over the course of 10 minutes, and the reaction was heated a reflux for 2 hours. The reaction was absorbed onto silica and purified via flash chromatography using a (0348) DCM/MeOH gradient. The desired compound was isolated and dried, methyl 5-(7- chloroimidazo[l, 2-a]pyridin-3-yl)-3-(l-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2- carboxylate (0.067 mg, 30.7%).3-Bromo-7-chloro-imidazo-[1, 2-a]-pyridine (1 eq, 6.48 mmol, 1.5 g) and 2-chloro- pyridine-4-boronic acid (1 eq, 6.48 mmol, 1.02 g) are dissolved in DME (6 ml) and water (2 ml) and Na2CO3 (2 eq, 13.0 mmol, 1.61 g) is added. PdCl2(PPh3J2 (0.06 eq, 0.389 mmol, 273 mg) is added and the reaction mixture is heated using microwave radiation at 120C for 10 min. At the completion of this time the solvent is removed in vacuo and the reaction mixture is purified by flash column chromatography eluting with 8:2 DCM/MeOH to yield 7-chloro-3-(2-chloro-pyridin-4-yl)-imidazo[1, 2- ajpyridine as an orange solid; [M+H]+ = 2657-Chloro-imidazo-[1, 2-a]-pyridine (1 eq, 38.9 mmol, 5.93 g) is dissolved in DMF (20 ml) at 0C and NBS (1.1 eq, 42.8 mmol, 7.61 g) is added. The reaction mixture is stirred for Ih at 0C and is diluted with EtOAc. The reaction mixture is washed with NaHCO3 and brine, dried over MgStheta4, filtered and evaporated. The product is purified by flash column chromatography eluting with 8:2 DCM/MeOH to afford 3- bromo-7-chloro-imidazo-[1, 2-a]-pyridine as a brown solid; [M+H]+ = 2323-Bromo-7-chloro-imidazo-[1, 2-a]-pyridine (1 eq, 2.59 mmol, 600 mg) and 3-(1H- pyrazolyl)-phenylboronic acid (1.2 eq, 1.04 mmol, 195 mg) are dissolved in DME (5 ml) and water (1.5 ml) and Na2CO3 (0.65 eq, 1.68 mmol, 209 mg) is added. PdCl2(PPh3)2 (0.04 eq, 0.104 mmol, 72.8 mg) is added and the reaction mixture is heated using microwave radiation at 120C for 10 min. At the completion of this time 3-Bromo-7-chloro-imidazo[1, 2-a]pyridine (1 eq, 3.02 mmol, 700 mg) and 2, 6- dichloro-4-(4, 4, 5, 5-tetramethyl-[1, 3, 2]dioxaborolan-2-yl)-pyridine (1.1 eq, 3.32 mmol, 1.01 g) are dissolved in DME (4 ml) and water (1 ml) and Na2COs (1.5 eq, 5.53 mmol, 562 mg) is added. PdCl2(PPh3J2 (0.1 eq, 0.3 mmol, 212 mg) is added and the reaction mixture is heated using microwave radiation at 120C for 15 min. At the completion of this time the solvent is removed in vacuo and the reaction mixture is purified by flash column chromatography eluting with 9:1 DCM/MeOH to yield 7-chloro-3-(2, 6- dichloro-pyridin-4-yl)-imidazo[1, 2-a]pyridine as a yellow solid; [M+H]+ = 299

Molecular Weight:231.48
XLogP3:3.4
Hydrogen Bond Acceptor Count:1
Exact Mass:229.92464
Monoisotopic Mass:229.92464
Topological Polar Surface Area:17.3
Heavy Atom Count:11
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes