[ClH:1].[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[C:16](=[O:17])[CH:15]=[N:14][C:13]3[CH:18]=[CH:19][C:20]([O:22][CH3:23])=[N:21][C:12]2=3)[CH2:5][CH2:4]1.[O:24]=[C:25]1[NH:36][C:29]2[N:30]=[C:31]([CH:34]=O)[N:32]=[CH:33][C:28]=2[CH2:27][CH2:26]1.C([O-])(O)=O.[Na+].[O-]S([O-])(=O)=O.[Na+].[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CO.[CH2:65]([Cl:67])[Cl:66]>>[CH2:65]([Cl:67])[Cl:66].[CH2:65]([Cl:67])[Cl:66].[CH3:16][OH:17].[NH4+:2].[OH-:24].[ClH:1].[CH3:23][O:22][C:20]1[CH:19]=[CH:18][C:13]2[N:14]=[CH:15][C:16](=[O:17])[N:11]([CH2:10][CH2:9][N:6]3[CH2:5][CH2:4][CH:3]([NH:2][CH2:34][C:31]4[NH:30][C:29]5=[N:36][C:25](=[O:24])[CH2:26][CH2:27][C:28]5=[CH:33][N:32]=4)[CH2:8][CH2:7]3)[C:12]=2[N:21]=1To a solution of 4-[2-(4-amino-1-piperidinyl)ethyl]-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one hydrochloride (see Example 126(m) for a preparation) (0.600 g, 1.98 mmol) in 1:1 MeOH/DCM, was added 7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-carbaldehyde (0.350 g, 1.98 mmol), NaHCO3 (0.831 g, 9.90 mmol), and excess Na2SO4. The solution was stirred at ambient temperature overnight, followed by the addition of NaBH(OAc)3 (1.68 g, 7.92 mmol). The resulting solution was stirred for an additional 1 h, then concentrated onto silica gel under vacuum and the crude residue purified by column chromatography (silica gel) using a DCM/DCM-MeOH—NH4OH (90:10:1) gradient, followed by a further purification using 10% MeOH/DCM and then DCM/DCM-MeOH—NH4OH (90:1:0.1) to yield the free base of the desired product (0.396 g, 43%). LCMS: m/z 465.2 (MH+). 1H NMR (400 MHz, CDCl3) δ 1.42-1.53 (m, 2H) 1.90 (d, J=10.86 Hz, 2H) 2.18 (t, J=10.61 Hz, 2H) 2.52-2.60 (m, 1H) 2.66-2.77 (m, 5H) 2.93 (t, J=7.71 Hz, 2H) 3.07 (d, J=11.62 Hz, 2H) 3.98 (s, 2H) 4.00-4.03 (m, 3H) 4.52-4.62 (m, 2H) 6.70 (d, J=8.84 Hz, 1H) 7.99 (d, J=8.59 Hz, 1H) 8.12 (s, 1H) 8.34 (s, 1H).
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