4-Bromo-2-cyclopropylpyridine

i4-Bromo-2-cyclopropylpyridineTo a solution of 2, 4-dibromopyridine (3 g, 12.66 mmol) in dry tetrahydrofuran (10 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.435 g, 0.38 mmol).Cyclopropylzinc(II) bromide, 0.5M in tetrahydrofuran (30.1 mL, 15.05 mmol) was added over a period of 10 minutes. The reaction mixture was stirred at rt for 80 min. Additional cyclopropylzinc(II) bromide, 0.5M in tetrahydrofuran (7.52 mL, 3.76 mmol), was added and the reaction mixture was stirred for another 40 min before it was poured into saturated aqueous NaHCOTo a solution of 2, 4-dibromopyridine (0.500 g, 2.111 mmol) in tetrahydrofuran (5 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.073 g, 0.063 mmol). The reaction mixture was cooled to 0 °C, then cyclopropylzinc bromide, 0.5M in THF (12.66 mL, 6.33 mmol) was added dropwise over 10 min. The reaction mixture was stirred at 20 °C for 16 h. The reaction mixture was quenched with of 10percent NaHC0To a solution of To a solution of 4-bromo-2-cyclopropyl-pyridine (512 mg, 2.59 mmol, CAS1086381-28-3) and ethyl oxazole-4-carboxylate (365 mg, 2.59 mmol, CAS170487-38-4) in DMF (5 mL) was added tris-o-tolylphosphane (157 mg, 517 umol), Pd(OAc)2 (58.0 mg, 259 umol) and Cs2CO3 (1.68 g, 5.17 mmol). The reaction mixture was stirred at 70 C. for 12 hours under nitrogen. On completion, the reaction mixture was diluted with EA (100 mL), poured into sat.NH4Cl (50 mL) and extracted with EA (3×50 mL). The combined organic layers were washed with brine (50 mL), dried with anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica column chromatography (PE/EA, 10/1 to 5/1) to give the title compound (380 mg, 55% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) delta 8.57 (d, J=4.8 Hz, 1H), 8.33 (s, 1H), 7.82 (s, 1H), 7.67 (dd, J=1.6, 5.2 Hz, 1H), 4.44 (q, J=7.2 Hz, 2H), 2.16-2.07 (m, 1H), 1.42 (t, J=7.2 Hz, 3H), 1.12-1.02 (m, 4H). LC-MS (ESI+) m/z 259.1 (M+H)+.[0609] Step 1: 3-chloro-4-(2'-[3, 4'-bipyridin]-5-yl)aniline. A stirred solution of To a solution of To a mixture of tert-butyl 5-[tert- butoxycarbonyl-(l-tert-butoxycarbonyl-4, 5-dimethyl-pyrazole-3-carbonyl)amino]-2-(4, 4, 5, 5-tetramethyl- l, 3, 2-dioxaborolan-2-yl)pyrrolo[2, 3-b]pyridine- l-carboxylate 137 (1 eq.), 4-bromo-2-cyclopropyl- pyridine 134 (1 eq.), [l, r-bis(diphenylphosphino)ferrocene]dichloropalladium(ii) or tetrakis(trip enyp osp me)palladium(0) (0.1 eq.) in an appropriate amount of solvent (e. g. acetonitrile or tetrahydrofuran, or dioxane) is added an appropriate amount of aqueous potassium carbonate solution (1M). The reaction mixture is irradiated in microwave at temperature ranging from 90 to 180 C for 10 minutes to 2-3 hours. The reaction mixture is partitioned between water and an appropriate solvent (ethyl acetate or dichloromethane). The organic layer is collected, washed with brine and dried under sodium sulfate. After removal of drying agent and solvent, the residue is purified by chromatography to provide compound 138.To a mixture of 4, 5-dimethyl-N-[2-(4, 4, 5, 5- tetramethyl- l, 3, 2-dioxaborolan-2-yl)- lH-pyrrolo[2, 3-b]pyridin-5-yl]- lH-pyrazole-3-carboxamide 133 (1 eq.), 4-bromo-2-cyclopropyl-pyridine 134 (1 eq.), [Iota , Gamma- bis(diphenylphosphino)ferrocene]dichloropalladium(ii) or tetrakis( np enylphosp me)palladium(Q) (0.1 eq.) in an appropriate amount of solvent (e. g. acetonitrile or tetrahydrofuran, or dioxane) is added an appropriate amount of aqueous potassium carbonate solution (1M). The reaction mixture is irradiated in microwave at a temperature ranging from 90 C to 180 C for about 10 minutes to 2-3 hours. The reaction mixture is partitioned between water and an organic solvent (including, but not limiting to, hexanes, ethyl acetate and dichloromethane). The organic layer is collected, washed by brine and dried under sodium sulfate. After removal of drying agent and solvent, the residue was purified by chromatography to provide compound 135.

Molecular Weight:198.06
XLogP3:2.1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:196.98401
Monoisotopic Mass:196.98401
Topological Polar Surface Area:12.9
Heavy Atom Count:10
Complexity:122
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes