Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](Br)[CH:5]=[CH:4][N:3]=1.[CH3:9][NH:10][C@@H:11]1[CH2:15][CH2:14][NH:13][CH2:12]1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[CH:7]=[C:6]([N:13]2[CH2:14][CH2:15][C@@H:11]([NH:10][CH3:9])[CH2:12]2)[CH:5]=[CH:4][N:3]=1
Reactant: Clc1cc(Br)ccn1
Reactant: CN[C@@H]1CCNC1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: O
Solvent: Cc1ccccc1
Product: CN[C@@H]1CCN(c2ccnc(Cl)c2)C1
Temperature: 85 °C
Yield: 30.6 %

Procedure:
To a stirring solution of 2-chloro-4-bromopyridine (4.3 g, 22.1 mmol) in toluene (100 mL) was added (R)-methyl-pyrrolidin-3-yl-amine (1.7 g, 17.0 mmol) and sodium tert-butoxide (2.5 g, 26.0 mmol). The flask was evacuated and flushed with N2(g) twice. A mixture of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 590 mg, 1.0 mmol) and tris(dibenzylideneacetone)-dipalladium(0) (Pd2(dba)3; 310 mg, 0.34 mmol) was added in one portion and the mixture was heated at 85° C. for 20 h. The mixture was cooled to room temperature (rt), diluted with H2O (75 mL), and extracted with ethyl acetate (EtOAc; 3×). The combined organic layers were dried and concentrated to give a clear brown oil. The oil was purified by FCC (0 to 5% 2 M NH3 in MeOH/CH2Cl2) to give the title compound as a brown solid (1.1 g, 30%). MS (ESI): mass calcd. for C10H14ClN3, 211.09 m/z found, 212.1 [M+H]. 1H NMR (DMSO-d6): 7.86 (d, J=5.9, 1H), 6.47-6.38 (m, 2H), 3.45-3.17 (m, 4H), 3.11-3.01 (m, 1H), 2.29 (s, 3H), 2.15-2.00 (m, 1H), 1.82 (br s, 1H), 1.79-1.65 (m, 1H). Bicyclo[2.2.1]hept-2-yl-[(3R)-4-(3-methylamino-pyrrolidin-1-yl)-pyridin-2-yl]-amine. To a stirring mixture of [(3R)-1-(2-chloro-pyridin-4-yl)-pyrrolidin-3-yl]-methyl-amine (97 mg, 0.46 mmol), exo-2-aminonorbornane (164 μL, 1.4 mmol) in ethylene glycol dimethyl ether (DME; 4 mL) in a scintillation vial was added sodium tert-butoxide (245 mg, 2.6 mmol). To the stirring mixture was added in one portion Pd(OAc)2 (16 mg, 0.024 mmol) and racemic 2,2′-bis(diphenylphosphino)-1,1′-bihaphthyl (BINAP; 19 mg, 0.031 mmol). The mixture was heated at 65° C. for 20 h, then was cooled to rt and filtered through a plug of diatomaceous earth. The plug was washed with MeOH (2 mL) and the filtrate was purified directly by FCC (5% 2 M NH3 in MeOH/CH2Cl2) to give a clear light golden oil (70 mg, 54%). Bicyclo[2.2.1]hept-2-yl-[(3R)-4-(3-methylamino-pyrrolidin-1-yl)-pyridin-2-yl]-amine. To a stirring solution of bicyclo[2.2.1]hept-2-yl-[(3R)-4-(3-methylamino-pyrrolidin-1-yl)-pyridin-2-yl]-amine in 1:1 Et2O/CH2Cl2 (8 mL) was added 1 N HCl in Et2O (1 mL). The organic layers was separated and concentrated to give the desired product (89 mg, 100%) as a beige solid. MS (ESI): mass calcd. for C17H26N4, 286.2; m/z found, 287.3 [M+H]+. 1H NMR (DMSO-d6): 12.07 (s, 1H), 9.57 (br s, 1H), 9.46 (br s, 1H), 7.81 (d, J=5.1, 1H), 7.66 (d, J=4.6, 1H), 6.28 (d, J=7.4, 1H), 5.64 (s, 1H), 3.89 (br s, 1H), 3.85-3.61 (m, 3H), 3.49 (br s, 2H), 2.60 (s, 3H), 2.35-2.20 (m, 3H), 2.18 (s, 1H), 1.95-1.85 (m, 1H), 1.55-1.46 (m, 3H), 1.37-1.25 (m, 2H), 1.21-1.09 (m, 2H). The compounds in Example 2 through Example 15 were prepared using methods analogous to those described for Example 1.