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

HRID 1838872Notes

Reaction equation

HRID 1838872 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:27](=[O:36])[CH2:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[N:15]([CH3:26])[C:16]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([S:24][CH3:25])[N:19]=2)=O)[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](=[O:36])[C:28]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)=[C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([S:24][CH3:25])[N:19]=3)[N:15]2[CH3:26])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 600611404-{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 600611414-[4-(4-Fluorophenyl)-2-methyl-3-(2-methylsulfanyl-pyrimidin-4-yl)-5-oxo-2,5-dihydro-pyrazol-1-yl]-piperidine-1 carboxylic acid tert-butyl esterYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. 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, 17, (26.7 g, 51.7 mmol) in DMF (50 mL) is slowly added NaH (3.1 g of a 60% dispersion in mineral oil, 77.55 mmol). The reaction mixture is stirred for 0.5 h at 0° C. and then quenched with 1.0 N HCl. The aqueous layer is extracted threee times with CH2Cl2. The combined organic layers are dried (MgSO4), filtered and concentrated in vacuo. Purification over silica (100% EtOAc) affords 12 g (45% yield) of the desired product: 1H NMR (300 MHz, CDCl3) δ 8.50 (d, J=4.9 Hz, 1H), 7.35-7.29 (m, 2H), 7.02 (t, J=6.8 Hz, 2H), 6.85 (d, J=5.1 Hz, 1H), 4.42-4.32 (m, 3H), 3.28 (s, 3H), 2.88 (t, 12.8 Hz, 2H), 2.58 (s, 3H), 2.79-2.39 (m, 2H), 1.94 (d, J=11.7 Hz, 2H), 1.50 (s, 9H); ESI/MS: 500.3 (M+H).

Workup

  1. customTo a 0° C.
  2. customquenched with 1.0 N HCl
  3. extractionThe aqueous layer is extracted threee times with CH2Cl2
  4. dry with materialThe combined organic layers are dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification over silica (100% EtOAc)

Sources & evidence

ORD record
ord-085982766d2c4cd791a52c9d47ee345a
Source dataset
uspto-grants-2004_01
Patent number
US06677337B2

Reaction notes

Loading…