Cesium carbonate → tert-Butyl 6-[(1-methyl-1H-pyrazol-5-yl)amino]-4-oxo-spiro[chroman-2,4'-piperidine]-1'-carboxylate

HRID 420170Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:21](=[CH:22][CH:23]=1)[O:20][C:7]1([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)[CH2:6][C:5]2=[O:24].[NH2:25][C:26]1[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:31][N:30]1[C:26]([NH:25][C:2]2[CH:3]=[C:4]3[C:21](=[CH:22][CH:23]=2)[O:20][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][C:5]3=[O:24])=[CH:27][CH:28]=[N:29]1

Participants

Conditions

Temperature: 110 °C

Procedure

tert-Butyl 6-bromo-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (16.3 g), 5-amino-1-methyl-1H-pyrazole (4.00 g), palladium acetate (922 mg), 2-(di-t-butylphosphino)biphenyl (1.23 g) and cesium carbonate (16.1 g) were suspended in 1,4-dioxane (20 mL), and heated under reflux at 110° C. for 5 hours. The reaction liquid was filtered through Celite, the residue on the Celite was washed with chloroform, and the filtrate was concentrated under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane/EtOAc) to obtain the intended compound as a yellow amorphous substance.

Workup

temperatureheated
customThe reaction liquid
filtrationwas filtered through Celite
washthe residue on the Celite was washed with chloroform
concentrationthe filtrate was concentrated under reduced pressure
customThe resulting residue was purified through silica gel column chromatography (hexane/EtOAc)
customto obtain the intended compound as a yellow amorphous substance

Sources & evidence

ORD record: ord-4399e7e8e3ee4eda82596495c9ca5389
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093389B2

Reaction notes

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