Sodium hydride → 2,2-dimethyl-propionic acid 6-(4-fluorophenyl)-7-(2-methylsulfanyl-pyrimidin-4-yl)-5-oxo-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl ester

HRID 2052875Notes

Reaction equation

HRID 2052875 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]2[CH2:15][CH:14]([O:16][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:13][N:12]2[C:23]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([S:31][CH3:32])[N:26]=2)=O)=[O:10])=[CH:4][CH:3]=1.[H-].[Na+]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9](=[O:10])[N:11]3[CH2:15][CH:14]([O:16][C:17](=[O:22])[C:18]([CH3:19])([CH3:21])[CH3:20])[CH2:13][N:12]3[C:23]=2[C:25]2[CH:30]=[CH:29][N:28]=[C:27]([S:31][CH3:32])[N:26]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 207247342,2-Dimethyl-propionic acid 1-[2-(4-fluorophenyl)acetyl]-2-(methylsulfanyl-pyrimidine-4-carbonyl)-pyrazolidin-4-yl ester

Product 1

HCID 207247402,2-dimethyl-propionic acid 6-(4-fluorophenyl)-7-(2-methylsulfanyl-pyrimidin-4-yl)-5-oxo-2,3-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl esterYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2,2-Dimethyl-propionic acid 1-[2-(4-fluorophenyl)acetyl]-2-(methylsulfanyl-pyrimidine-4-carbonyl)-pyrazolidin-4-yl ester, 33, (300 mg, 0.651 mmol) is dissolved in THF (6 mL). This solution is then added dropwise via cannula to a suspension of NaH (29 mg of a 60% dispersion in mineral oil, 0.716 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.) (1 mL). The mixture is stirred at room temperature, then concentrated in vacuo. The residue is diluted with tetrahydrofuran (50 mL) and the mixture filtered through Celite. The filtrate is concentrated in vacuo to give an orange oil. The crude product is purified over silica (100% ethyl acetate to 5% to 10% to 20% methyl alcohol/ethyl acetate) to afford 87 mg (30% yield) of the desired product as a yellow solid.

Workup

  1. customThe reaction is quenched with NH4Cl (sat. aq.) (1 mL)
  2. concentrationconcentrated in vacuo
  3. additionThe residue is diluted with tetrahydrofuran (50 mL)
  4. filtrationthe mixture filtered through Celite
  5. concentrationThe filtrate is concentrated in vacuo
  6. customto give an orange oil
  7. 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-0975cc02a8ae42309c3a297e7b3b2483
Source dataset
uspto-grants-2008_02
Patent number
US07326714B2

Reaction notes

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