[CH3:1][C:2]1([CH3:12])[CH2:10][CH:9]([NH2:11])[CH2:8][CH:7]2[N:3]1[CH2:4][CH2:5][CH2:6]2.[Cl:13][C:14]1[N:19]=[C:18](Cl)[C:17]([C:21]([NH2:23])=[O:22])=[CH:16][N:15]=1.O>CO>[Cl:13][C:14]1[N:19]=[C:18]([NH:11][CH:9]2[CH2:8][CH:7]3[N:3]([CH2:4][CH2:5][CH2:6]3)[C:2]([CH3:12])([CH3:1])[CH2:10]2)[C:17]([C:21]([NH2:23])=[O:22])=[CH:16][N:15]=1A mixture of (±)-octahydro-5,5-dimethylindolizin-7-amine (0.65 g, 3.9 mmol) in MeOH (10 ml) was added to a stirred solution of 2,4-dichloropyrimidine-5-carboxamide (0.75 g, 3.9 mmol; prepared according to the procedure set forth in US patent application publication US20110130415, page 41) in MeOH (30 ml) and H2O (4 ml) at 0° C. under nitrogen. After complete addition, the mixture was slowly warmed to room temperature and stirred at room temperature overnight. The mixture was then concentrated in vacuo and the residue partitioned between EtOAc (150 ml) and 1N NaOH (100 ml). The aqueous layer was extracted with EtOAc (1×100 ml) and the combined organic extracts were dried (Na2SO4), filtered and the solvent removed in vacuo. The residue was dry-loaded on to basic alumina (Brockmann grade IV) and then purified by column chromatography on basic alumina (Brockmann grade IV) using CH2Cl2/MeOH (1:0 to 95:5) as eluent to give the product (550 mg).
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