2-BROMO-4-PYRROLIDIN-1-YL-PYRIDINE

Preparation 742-Bromo-4-pyrrolidin-1-ylpyridine2, 4-Dibromopyridine (300mg, 0.94mmol) and pyrrolidine (335mg, 4.7mmol) were combined in ethanol and heated at 702, 4-Dibromopyridine (1.0 g, 4.22 mmol) was dissolved in ethanol (40 mL) and pyrrolidine (1.733 ml, 21 .11 mmol) was added. The reaction mixture was stirred at 70 °C for 20 hours. The reaction mixture was cooled to room temperature and the solvent was removed in vacuo to give a pale yellow solid. The crude product was purified by chromatography on silica gel (gradient: 0-80percent ethyl acetate in isohexane) to afford 2-bromo-4-(pyrrolidin- 1 -yl)pyridine (460 mg) as a white solid, and 4-bromo-2-(pyrrolidin-l -yi)pyridine (260 mg) as a white solid. LCMS (Method F, ES-API): RT 0.79 min, m+H = 227.1/229.1.2, 4-Dibromopyridine (1.0 g, 4.22 mmol) was dissolved in ethanol (40 mL) and pyrrolidine (1.733 ml, 21 .11 mmol) was added. The reaction mixture was stirred at 70 C for 20 hours. The reaction mixture was cooled to room temperature and the solvent was removed in vacuo to give a pale yellow solid. The crude product was purified by chromatography on silica gel (gradient: 0-80% ethyl acetate in isohexane) to afford 2-bromo-4-(pyrrolidin- 1 -yl)pyridine (460 mg) as a white solid, and 4-bromo-2-(pyrrolidin-l -yi)pyridine (260 mg) as a white solid. LCMS (Method F, ES-API): RT 0.79 min, m+H = 227.1/229.1.General procedure: Chiral diamine (2.67 mmol), 2-bromo-4-alkylaminopyridine (5.88 mmol), NaOtBu (16 mmol), BINAP (0.11 mmol), and Pd(dba)2.CHCl3 (0.11 mmol) were mixed in 45 mL of toluene (which was distilled under Ar over Na-benzophenone) under an inert atmosphere. The mixture was heated to 110 C for 12 h, brought to rt, and transferred to a separatory funnel. The toluene phase was washed with 50 mL of water, after which the two phases were separated. The remaining water phase was washed with CH2Cl2 and the combined organic phases were concentrated under vacuum. The mixture was purified by flash chromatography; the solvent polarity was gradually changed from pure EtOAc to 20:1 EtOAc:NEt3 with each 100 mL mobile phase portion.Example 5 2, 2-Dimethyl-1-[2-(4-pyrrolidin-1-yl-pyridin-2-yl)-5-(2-timethylsilanyl-ethoxymethyl)-5H-pyrrolo[2, 3-b]pyrazin-7-yl]-propan-1-one To THF (1 mL) at -78 C. was added dropwise a solution of t-BuLi (0.78 mL, 1.3 M solution in pentane, 1 mmol). To the resultant yellow solution was added dropwise a brown solution of Example 5 2, 2-Dimethyl-1-[2-(4-pyrrolidin-1-yl-pyridin-2-yl)-5-(2-timethylsilanyl-ethoxymethyl)-5H-pyrrolo[2, 3-b]pyrazin-7-yl]-propan-1-one To THF (1 mL) at -78 C. was added dropwise a solution of t-BuLi (0.78 mL, 1.3 M solution in pentane, 1 mmol). To the resultant yellow solution was added dropwise a brown solution of Preparation 742-Bromo-4-pyrrolidin-1-ylpyridine2, 4-Dibromopyridine (300mg, 0.94mmol) and pyrrolidine (335mg, 4.7mmol) were combined in ethanol and heated at 700C overnight. The reaction mixture was concentrated in vacuo and the residue purified by column chromatography using an ISCO silica cartridge eluting with 0- 70% ethyl acetate: pentane. (208mg, 0.91 mmol, 97%).1H-NMR (CDCI3, 400MHz): delta 2.0 (m, 4H), 3.3 (m, 4H), 6.3 (m, 1 H), 6.6 (s, 1 H)1 7.9 (d, 1 H). LRMS m/z (APCI) 227 [MH]+.

Molecular Weight:227.10
XLogP3:2.5
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:226.01056
Monoisotopic Mass:226.01056
Topological Polar Surface Area:16.1
Heavy Atom Count:12
Complexity:146
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes