Nitrogen → 2-chloro-4-(3,5-dimethyl-isoxazol-4-yl)-6,7-dihydro-5H-cyclopentapyrimidine

HRID 1668829Notes

Reaction equation

[CH3:1][C:2]1(B(O)O)[CH:6]=[C:5]([CH3:7])[O:4][NH:3]1.[Cl:11][C:12]1[N:17]=[C:16](Cl)[C:15]2[CH2:19][CH2:20][CH2:21][C:14]=2[N:13]=1.N#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:11][C:12]1[N:17]=[C:16]([C:6]2[C:2]([CH3:1])=[N:3][O:4][C:5]=2[CH3:7])[C:15]2[CH2:19][CH2:20][CH2:21][C:14]=2[N:13]=1

Participants

Conditions

Temperature: 27.5 °C

Procedure

3,5-Dimethylisoxazole boronic acid (0.4 g, 2.8 mmol) was added to a solution of 2,4-dichloro-6,7-dihydro-5H-cyclopentapyrimidine (0.75 g, 4 mmol) in tetrahydrofuran (10 mL). The mixture was flushed with N2 before addition of palladium acetate (0.07 g, 0.28 mmol) and triphenylphosphine (0.14 g, 0.56 mmol). Thereafter, 2M aqueous sodium carbonate solution was added and the mixture was reflushed with N2. The mixture was stirred at a temperature in the range of 20° C. to 50° C. for 8 to 12 hours and then cooled to about 20 to 35° C. The mixture was diluted with water and the organic layer was separated. The aqueous layer was re-extracted with ethyl acetate. The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by column chromatography (silica gel) to afford the title compound as a light yellow liquid (0.52 g, 53% yield).

Workup

customthe organic layer was separated
extractionThe aqueous layer was re-extracted with ethyl acetate
washwashed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude residue was purified by column chromatography (silica gel)

Sources & evidence

ORD record: ord-2ba438119aa04ebb87a31aa3afc2cb71
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989463B2

Reaction notes

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