Sodium hydride → 4-[4-(4-Fluorophenyl)-2-methyl-5-(2-methylsulfanyl-pyrimidin-4-yl)-3-oxo-2,3-dihydro-pyrazol-1-yl]-piperidine-1 carboxylic acid tert-butyl ester

HRID 1838866Notes

Reaction equation

HRID 1838866 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:27]([C:29]2[CH:34]=[CH:33][N:32]=[C:31]([S:35][CH3:36])[N:30]=2)=O)[N:15]([C:17](=[O:26])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:27]([C:29]3[CH:34]=[CH:33][N:32]=[C:31]([S:35][CH3:36])[N:30]=3)=[C:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:17](=[O:26])[N:15]2[CH3:16])[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 115916664-{N'-[2-(4-fluoro-phenyl)-acetyl]-N'-methyl-N-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 116989724-[4-(4-Fluorophenyl)-2-methyl-5-(2-methylsulfanyl-pyrimidin-4-yl)-3-oxo-2,3-dihydro-pyrazol-1-yl]-piperidine-1 carboxylic acid tert-butyl esterYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-{N′-[2-(4-fluoro-phenyl)-acetyl]-N′-methyl-N-(2-methylsulfanyl-pyrimidine-4-carbonyl)-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester, 10, (1.058 g, 2.05 mmol) in DMF (2 mL) at 0° C. is slowly added NaH (123 mg of a 60% dispersion in mineral oil, 3.07 mmol). The reaction mixture is stirred for 1 hour at 0° C. and then quenched with 0.1 N HCl. The aqueous layer is extracted three times with CH2Cl2 and the combined organic layers are dried (MgSO4), filtered and concentrated in vacuo. Purification over silica (20% MeOH/CHCl3) affords 0.743 g (73% yield) of the diesired product. ESI/MS: 500.2 (M+H).

Workup

  1. customat 0° C.
  2. customquenched with 0.1 N HCl
  3. extractionThe aqueous layer is extracted three times with CH2Cl2
  4. dry with materialthe combined organic layers are dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification over silica (20% MeOH/CHCl3)

Sources & evidence

ORD record
ord-49c3eb574f1145b99b263ed126517b79
Source dataset
uspto-grants-2004_01
Patent number
US06677337B2

Reaction notes

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