Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](Br)[CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].CC(C)([O-])C.[Na+]>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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]
Reactant: Clc1cc(Br)ccn1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCN(c2ccnc(Cl)c2)CC1
Temperature: 85 °C
Yield: 99.6 %

Procedure:
To a stirring solution of 2-chloro-4-bromopyridine (4.3 g, 22.5 mmol) in toluene (100 mL) was added piperazine-1-carboxylic acid tert-butyl ester (3.2 g, 17.2 mmol) and sodium tert-butoxide (2.5 g, 26.0 mmol). The flask was evacuated and flushed with N2(g) twice. A mixture of Xantphos (600 mg, 1.0 mmol) and Pd2(dba)3 (318 mg, 0.35 mmol) was added in one portion and the mixture was heated at 85° C. for 20 h. The mixture was cooled to rt, diluted with H2O (75 mL), and extracted with EtOAc (3×). The combined organic layers were dried and concentrated to give a clear golden oil. The oil was purified on FCC (0 to 5% 2 M NH3 in MeOH/CH2Cl2) to give the title product as a beige solid (5.1 g, 100%). MS (ESI): mass calcd. for C14H20ClN3O2, 297.1; m/z found, 298.2 [M+H]+. 1H NMR (DMSO-d6): 7.95 (d, J=5.9, 1H), 6.88-6.78 (m, 2H), 3.46-3.32 (m, 8H), 1.42 (s, 9H). tert-Butyl 4-[2-(cyclopentylamino)pyridin-4-yl]piperazine-1-carboxylate. To a stirring solution of 4-(2-chloro-pyridin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (163 mg, 0.55 mmol) in toluene (2 mL) in a vial was added cyclopentylamine (136 μL, 1.38 mmol) and sodium tert-butoxide (161 mg, 1.68 mmol). A mixture of racemic BINAP (20 mg, 0.032 mmol) and Pd(OAc)2 (18 mg, 0.027 mmol) was added in one portion and the mixture was heated at 85° C. for 20 h. The mixture was cooled to rt and purified directly by FCC (0 to 5% 2 M NH3 in MeOH/CH2Cl2) to provide the title compound as a white solid (34 mg, 17%). MS (ESI): mass calcd. for C16H30N4O2, 346.2; m/z found, 347.3 [M+H]+. 1H NMR (DMSO-d6): 7.65 (d, J=6.0, 1H), 6.10 (d, J=6.0, 1H), 5.92 (d, J=7.1, 1H), 5.78 (s, 1H) 4.08-4.02 (m, 1H), 3.41 (t, J=5.4, 4H), 3.16 (t, J=5.4, 4H), 1.89-1.82 (m, 2H), 1.67-1.61 (m, 2H), 1.59-1.48 (m, 2H), 1.42 (s, 9H), 1.43-1.35 (m, 2H). N-Cyclopentyl-4-piperazin-1-ylpyridin-2-amine dihydrochloride. To a stirring solution of tert-butyl 4-[2-(cyclopentylamino)pyridin-4-yl]piperazine-1-carboxylate (34 mg, 0.1 mmol) in 96% formic acid (4 mL) was added 6 N aq HCl (2 drops). The mixture was stirred for 2 h and concentrated to give the desired product as a white solid (26 mg, 93%). MS (ESI): mass calcd. for C14H22N4, 246.2; m/z found, 247.2 [M+H]+. 1H NMR (DMSO-d6): 9.32 (s, 2H), 7.89 (d, J=7.1, 1H), 7.69 (d, J=7.5, 1H), 6.58 (d, J=7.6, 1H), 6.04 (s, 1H), 4.03-3.96 (m, 1H), 3.73 (t, J=4.9, 4H), 3.20 (t, J=5.0, 4H), 2.03-1.95 (m, 2H), 1.73-1.68 (m, 2H), 1.64-1.52 (m, 2H), 1.50-1.42 (M, 2H). The compounds in Example 17 through Example 20 were prepared using methods analogous to those described for Example 16.