Potassium Carbonate → methyl 2-(3-iodo-4-(2-(methylthio)pyrimidin-4-yl)-1H-pyrazol-1-yl)-2-methylpropanoate

HRID 500735Notes

Reaction equation

[I:1][C:2]1[NH:6][N:5]=[CH:4][C:3]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([S:13][CH3:14])[N:8]=1.Br[C:16]([CH3:22])([CH3:21])[C:17]([O:19][CH3:20])=[O:18].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[I:1][C:2]1[C:3]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([S:13][CH3:14])[N:8]=2)=[CH:4][N:5]([C:16]([CH3:22])([CH3:21])[C:17]([O:19][CH3:20])=[O:18])[N:6]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture compound A (60 g, 0.19 mol) and methyl 2-bromo-2-methylpropanoate (102 g, 0.57 mol) in DMF (400 mL) was added freshly ground potassium carbonate (65 g, 0.47 mol) in one portion. The reaction mixture was stirred at 80° C. for 18 hours. LC-MS indicated the reaction was complete. The reaction mixture was filtered and the filtrate was partitioned between ethyl acetate (1200 mL) and brine (300 mL). The aqueous layer was extracted with EtOAc (2×500 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel chromatography using 5-30% EtOAc in petroleum ether as eluent to give compound B-49-1 (62 g, 78%) as syrup, which solidified on standing.

Workup

filtrationThe reaction mixture was filtered
customthe filtrate was partitioned between ethyl acetate (1200 mL) and brine (300 mL)
extractionThe aqueous layer was extracted with EtOAc (2×500 mL)
washThe combined organic layers were washed with brine
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated
customThe residue was purified by silica gel chromatography
customto give compound B-49-1 (62 g, 78%) as syrup, which

Sources & evidence

ORD record: ord-2fa69fb071a84a9cbb5de72e9913e30b
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772246B2

Reaction notes

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