Cl[C:2]1[CH:11]=[C:6]2[NH:7][CH2:8][CH2:9][CH2:10][N:5]2[C:4](=[O:12])[N:3]=1.[H-].[Na+].Br[CH2:16][C:17]([O:19]CC)=[O:18].[F:22][C:23]1[CH:24]=[C:25]([CH2:30][OH:31])[CH:26]=[CH:27][C:28]=1[F:29]>O1CCCC1>[F:22][C:23]1[CH:24]=[C:25]([CH:26]=[CH:27][C:28]=1[F:29])[CH2:30][O:31][C:2]1[CH:11]=[C:6]2[N:7]([CH2:16][C:17]([OH:19])=[O:18])[CH2:8][CH2:9][CH2:10][N:5]2[C:4](=[O:12])[N:3]=1To a solution of 8-chloro-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one (5 g, 26.9 mmol) in tetrahydrofuran (20 mL) was added sodium hydride (2.59 g, 108 mmol) at r.t. stirred for 10 minutes at r.t., then was added ethyl 2-bromoacetate (4.50 g, 26.9 mmol) and stirred for 2 h, and followed by addition of (3,4-difluoro phenyl)methanol (3.88 g, 26.9 mmol). The reaction mixture was stirred for 1 h at r.t., quenched by addition of water, and extracted by EtOAc. The aqueous phase was acidified to pH˜1 with HCl (1N), washed by EtOAc, then the aqueous phase was concentrated in vacuum, and the residual was washed by methanol and filtrated. The filtrate was concentrated to afford the title compound (3.1 g)
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