Sodium hydride → tert-butyl 8-(3,4-difluorophenethoxy)-6-oxo-2,3,4,6-tetrahydro-1H-pyrimido[1,6-a]pyrimidine-1-carboxylate

HRID 920445Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][OH:11])[CH:5]=[CH:6][C:7]=1[F:8].[H-].[Na+].Cl[C:15]1[CH:31]=[C:19]2[N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21][CH2:22][CH2:23][N:18]2[C:17](=[O:32])[N:16]=1>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[F:8])[CH2:9][CH2:10][O:11][C:15]1[CH:31]=[C:19]2[N:20]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:21][CH2:22][CH2:23][N:18]2[C:17](=[O:32])[N:16]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-(3,4-difluorophenyl)ethanol (221 mg, 1.400 mmol) in THF (5 mL) was added NaH (112 mg, 2.80 mmol) at 0° C. The reaction mixture was stirred for 10 min at 0° C., and then tert-butyl 8-chloro-6-oxo-2,3,4,6-tetrahydro-1H-pyrimido[1,6-a]pyrimidine-1-carboxylate (400 mg, 1.400 mmol) was added and stirred for another 0.5 hr at 0° C. The mixture was poured into ice water and extracted with DCM (10 mL×3). The combined extracts were washed with water (10 mL) then brine (10 mL) and then dried over Na2SO4. The mixture was concentrated to give tert-butyl 8-(3,4-difluorophenethoxy)-6-oxo-2,3,4,6-tetrahydro-1H-pyrimido[1,6-a]pyrimidine-1-carboxylate. A solution of the crude compound in 1,4-dioxane (10 mL) was added 4N HCl, stirred for 3 h at rt, and then concentrated. The residue was purified by MDAP to afford the HCl salt of the title product as a white solid (46 mg, 10.8% yield).

Workup

stirringstirred for another 0.5 hr at 0° C
extractionextracted with DCM (10 mL×3)
washThe combined extracts were washed with water (10 mL)
dry with materialbrine (10 mL) and then dried over Na2SO4
concentrationThe mixture was concentrated

Sources & evidence

ORD record: ord-32e3d0c745034d63b48591dee7f359ea
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273054B2

Reaction notes

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