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

HRID 570253Notes

Reaction equation

HRID 570253 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:17])([F:16])[F:15])[N:5]=[C:4]([NH2:18])[C:3]=1[N+:19]([O-:21])=[O:20].[H-].[Na+].[C:24]([C:28]1[CH:29]=[C:30]([C:34](Cl)=[O:35])[N:31]([CH3:33])[N:32]=1)([CH3:27])([CH3:26])[CH3:25]>C1COCC1>[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:15])([F:16])[F:17])[N:5]=[C:4]([NH:18][C:34]([C:30]2[N:31]([CH3:33])[N:32]=[C:28]([C:24]([CH3:26])([CH3:25])[CH3:27])[CH:29]=2)=[O:35])[C:3]=1[N+:19]([O-:21])=[O:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27356843-(Tert-Butyl)-1-Methyl-1H-Pyrazole-5-Carbonyl ChlorideHCID 674097756-Methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-ylamine

Product 1

HCID 674115755-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [6-methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 6-methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-ylamine (150 mg, 0.503 mmol, prepared as described in Example 2, STEP A) in THF (10 mL) was treated with NaH (60.4 mg, 1.51 mmol, 60% dispersion in oil), and the resulting mixture was allowed to stir for 30 min at room temperature. 5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl chloride (131 mg, 0.654 mmol) was added as a solution in THF (3 mL). After 15 min, the mixture was quenched with saturated aqueous NH4Cl (20 mL) and extracted twice with EtOAc (25 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 12-g SEPRA Si 50 SPE column (Isco system: Flow rate=15 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 10 min, then 1:99 to 1:4 v/v over 40 min) to yield 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [6-methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide as a colorless glassy solid. 1H-NMR (400 MHz, CDCl3) δ: 9.10 (s, 1H), 7.79-7.86 (m, 2H), 7.60-7.72 (m, 2H), 6.64 (s, 1H), 4.14 (s, 3H), 2.83 (s, 3H), 1.33 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C21H21F3N6O3: 463.2 (M+H); Measured: 463.2.

Workup

  1. waitAfter 15 min
  2. customthe mixture was quenched with saturated aqueous NH4Cl (20 mL)
  3. extractionextracted twice with EtOAc (25 mL)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 12-g SEPRA Si 50 SPE column (Isco system
  7. waitEluent=EtOAc/hexanes, 1:99 v/v for 10 min

Sources & evidence

ORD record
ord-161ca0930e364467866019e2a526ec7a
Source dataset
uspto-grants-2015_05
Patent number
US09023846B2

Reaction notes

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