Sodium hydride → 3-tert-butyl-4-chloro-N-(6-(2-chlorophenyl)-2-methoxy-3-nitropyridin-4-yl)-1-methyl-1H-pyrazole-5-carboxamide

HRID 1191251Notes

Reaction equation

HRID 1191251 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]([O:14][CH3:15])[C:11]([N+:16]([O-:18])=[O:17])=[C:10]([NH2:19])[CH:9]=1.[H-].[Na+].[C:22]([C:26]1[C:27]([Cl:35])=[C:28]([C:32](O)=[O:33])[N:29]([CH3:31])[N:30]=1)([CH3:25])([CH3:24])[CH3:23].C(Cl)(=O)C(Cl)=O>C1COCC1.C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]([O:14][CH3:15])[C:11]([N+:16]([O-:18])=[O:17])=[C:10]([NH:19][C:32]([C:28]2[N:29]([CH3:31])[N:30]=[C:26]([C:22]([CH3:24])([CH3:23])[CH3:25])[C:27]=2[Cl:35])=[O:33])[CH:9]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 584254493-tert-butyl-4-chloro-1-methyl-1H-pyrazole-5-carboxylic acidHCID 674116886-(2-Chlorophenyl)-2-methoxy-3-nitropyridin-4-amine

Product 1

HCID 674096383-tert-butyl-4-chloro-N-(6-(2-chlorophenyl)-2-methoxy-3-nitropyridin-4-yl)-1-methyl-1H-pyrazole-5-carboxamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-(2-chloro-phenyl)-2-methoxy-3-nitro-pyridin-4-ylamine (8.10 g, 29.0 mmol, prepared as described in the previous step) in THF (200 mL) was treated with NaH (3.47 g, 86.8 mmol, 60% dispersion in oil) at 0° C. for 1 h. Simultaneously a solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (6.90 g, 31.8 mmol, prepared as described in Example B) in DCM (200 mL) was treated with oxalyl chloride (3.2 mL, 36 mmol) and DMF (50 μl) at 0° C. and stirred at room temperature for 1 h. The volatile components were removed in vacuo, and the resulting residue was dried in vacuo for 15 min taken up in THF (20 mL) and added to the above sodium anilide solution at 0° C. The resulting mixture was stirred at room temperature for 30 min, quenched with saturated aqueous NH4Cl (20 mL), and extracted with EtOAc (3×100 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The resulting solid was suspended in hexane (200 mL) and sonicated for 10 min and collected by suction filtration to yield 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [6-(2-chloro-phenyl)-2-methoxy-3-nitro-pyridin-4-yl]-amide as a tan-colored solid.

Workup

  1. customThe volatile components were removed in vacuo
  2. customthe resulting residue was dried in vacuo for 15 min
  3. additionadded to the above sodium anilide solution at 0° C
  4. stirringThe resulting mixture was stirred at room temperature for 30 min
  5. customquenched with saturated aqueous NH4Cl (20 mL)
  6. extractionextracted with EtOAc (3×100 mL)
  7. dry with materialThe combined extracts were dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customsonicated for 10 min
  10. filtrationcollected by suction filtration

Sources & evidence

ORD record
ord-d4701b02707e455e9fc0ef963d89c1ac
Source dataset
uspto-grants-2014_03
Patent number
US08680098B2

Reaction notes

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