Ethyl 5-methyl-2,4-dioxohexanoate → ethyl 1-(2,4-dimethoxypyrimidin-5-yl)-5-isopropyl-1H-pyrazole-3-carboxylate

HRID 873887Notes

Reaction equation

[NH:1]([C:3]1[C:4]([O:11][CH3:12])=[N:5][C:6]([O:9][CH3:10])=[N:7][CH:8]=1)[NH2:2].[CH2:13]([O:15][C:16](=[O:25])[C:17](=O)[CH2:18][C:19](=O)[CH:20]([CH3:22])[CH3:21])[CH3:14]>C1(C)C=CC=CC=1>[CH3:10][O:9][C:6]1[N:5]=[C:4]([O:11][CH3:12])[C:3]([N:1]2[C:19]([CH:20]([CH3:21])[CH3:22])=[CH:18][C:17]([C:16]([O:15][CH2:13][CH3:14])=[O:25])=[N:2]2)=[CH:8][N:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

5-hydrazinyl-2,4-dimethoxypyrimidine (Step 46.8) (140 g, 823 mmol) was dissolved in toluene (3 L) under nitrogen atmosphere and ethyl-2,4-dioxo-5-methylhexanoate (230 g, 1234 mmol) was added dropwise over 15 min. The reaction mixture was heated up and stirred at 110° C. for 1 hr. The brown solution was quenched with saturated aq. NaHCO3 solution (2 L) and extracted with EtOAc (2×2 L). The combined organic layers were washed with brine (2 L), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was stirred in hexane (1 L) at RT and the resulting suspension was filtrated off and dried to afford the title product (193 g, 596 mmol, 72% yield) as white crystals. tR: 1.01 min (LC-MS 1); ESI-MS: 321 [M+H]+ (LC-MS 1).

Workup

temperatureThe reaction mixture was heated up
customThe brown solution was quenched with saturated aq. NaHCO3 solution (2 L)
extractionextracted with EtOAc (2×2 L)
washThe combined organic layers were washed with brine (2 L)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
stirringThe crude material was stirred in hexane (1 L) at RT
filtrationthe resulting suspension was filtrated off
customdried

Sources & evidence

ORD record: ord-93a144c0e443403ca4e4ee57a2d92e27
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08975417B2

Reaction notes

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