Sodium hydride → 6-dimethylamino-2-(4-fluorophenyl)-3-(2-methylsulfanyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

HRID 22677

Reaction equation

[CH3:1][N:2]([CH3:28])[CH:3]1[CH2:7][N:6]([C:8](=[O:17])[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[N:5]([C:18]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([S:26][CH3:27])[N:21]=2)=O)[CH2:4]1.[H-].[Na+]>C1COCC1>[CH3:1][N:2]([CH3:28])[CH:3]1[CH2:7][N:6]2[C:8](=[O:17])[C:9]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)=[C:18]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([S:26][CH3:27])[N:21]=3)[N:5]2[CH2:4]1

Participants

Conditions

Temperature: 0 °C

Procedure

1-[4-Dimethylamino-2-(2-methylsulfanyl-pyrimidine-4-carbonyl)-pyrazolidin-1-yl]-2-(4-fluorophenyl)-ethanone, 23, (4.0 g, 10 mmol) is dissolved in THF (75 mL). This solution is then added dropwise via cannula to a suspension of NaH (0.440 g of a 60% dispersion in mineral oil, 11 mmol) at −30° C. The reaction is allowed to gradually warm to 0° C. over 3 hours. The reaction is quenched with NH4Cl (sat. aq.) (15 ml ). The mixture is stirred at room temperature, then concentrated in vacuo. The residue is diluted with tetrahydrofuran (250 mL) and the mixture filtered through Celite. The filtrate is concentrated in vacuo to give an oil. The crude product is purified over silica (100% ethyl acetate to 5% to 10% to 20% methyl alcohol/ethyl acetate) to afford the desired product.

Workup

customThe reaction is quenched with NH4Cl (sat. aq.) (15 ml )
concentrationconcentrated in vacuo
additionThe residue is diluted with tetrahydrofuran (250 mL)
filtrationthe mixture filtered through Celite
concentrationThe filtrate is concentrated in vacuo
customto give an oil
customThe crude product is purified over silica (100% ethyl acetate to 5% to 10% to 20% methyl alcohol/ethyl acetate)

Sources & evidence

ORD record: ord-88766d1b325742c4b4a8a266c3502927
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06849627B2

Linked notes

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