Sodium hydride → 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide

HRID 1191219Notes

Reaction equation

HRID 1191219 reaction equation
[H-].[Na+].[C:3]([Si:7]([CH3:33])([CH3:32])[O:8][CH2:9][CH2:10][O:11][C:12]1[C:17]([N+:18]([O-:20])=[O:19])=[C:16]([NH2:21])[CH:15]=[C:14]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[C:28]([F:31])([F:30])[F:29])[N:13]=1)([CH3:6])([CH3:5])[CH3:4].[C:34]([C:38]1[C:39]([Cl:47])=[C:40]([C:44](Cl)=[O:45])[N:41]([CH3:43])[N:42]=1)([CH3:37])([CH3:36])[CH3:35]>C1COCC1>[C:3]([Si:7]([CH3:33])([CH3:32])[O:8][CH2:9][CH2:10][O:11][C:12]1[C:17]([N+:18]([O-:20])=[O:19])=[C:16]([NH:21][C:44]([C:40]2[N:41]([CH3:43])[N:42]=[C:38]([C:34]([CH3:36])([CH3:35])[CH3:37])[C:39]=2[Cl:47])=[O:45])[CH:15]=[C:14]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[C:28]([F:30])([F:31])[F:29])[N:13]=1)([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 674124792-[2-(Tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamineHCID 866574055-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carbonyl chloride

Product 1

HCID 674132015-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 60% sodium hydride in mineral oil (120 mg, 3.00 mmol) in THF (10 mL) at 0° C. was added 2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine (458 mg, 1.00 mmol, prepared as described in the previous step) slowly. The resulting mixture was warmed to room temperature and then stirred for 1 h under Ar. 5-tert-Butyl-4-chloro-2-methyl-2H-pyrazole-3-carbonyl chloride (259 mg, 1.10 mmol, prepared as described in Example 1, STEP C) was added and the resulting mixture was stirred for 3 h under Ar. After quenching with saturated aqueous NH4Cl solution (5 mL), the mixture was treated with EtOAc (100 mL) and washed with H2O, brine and dried with Na2SO4. Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (0:100-10:90 EtOAc/hexanes) yielded 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide as a white solid. 1H-NMR (400 MHz, CD3OD) δ: 10.10 (s, 1H), 8.33 (s, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.62-7.70 (m, 1H), 7.52-7.62 (m, 2H), 4.51-4.61 (m, 2H), 4.11 (s, 3H), 3.94-4.01 (m, 2H), 1.42 (s, 9H), 0.89 (s, 9H), 0.07 (s, 6H). Mass Spectrum (LCMS, ESI pos.) Calculated For C29H37ClF3N5O5Si: 656.2 (M+H), Measured: 656.2.

Workup

  1. customprepared
  2. stirringthe resulting mixture was stirred for 3 h under Ar
  3. customAfter quenching with saturated aqueous NH4Cl solution (5 mL)
  4. additionthe mixture was treated with EtOAc (100 mL)
  5. washwashed with H2O, brine
  6. dry with materialdried with Na2SO4
  7. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-02a72195720a409bb36cd35d42d0af1e
Source dataset
uspto-grants-2014_03
Patent number
US08680098B2

Reaction notes

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