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

HRID 1191203

Reaktionsgleichung

Reaktionsgleichung von HRID 1191203
[CH3:1][O:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[C:7]([NH2:12])[CH:6]=[C:5]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])[N:4]=1.[H-].[Na+].[C:25]([C:29]1[C:30]([Cl:38])=[C:31]([C:35](O)=[O:36])[N:32]([CH3:34])[N:33]=1)([CH3:28])([CH3:27])[CH3:26].C(Cl)(=O)C(Cl)=O>C1COCC1.C(Cl)Cl.CN(C=O)C>[CH3:1][O:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[C:7]([NH:12][C:35]([C:31]2[N:32]([CH3:34])[N:33]=[C:29]([C:25]([CH3:27])([CH3:26])[CH3:28])[C:30]=2[Cl:38])=[O:36])[CH:6]=[C:5]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:20])[F:21])[N:4]=1

Komponenten

8

Edukt 4

HCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 584254493-tert-butyl-4-chloro-1-methyl-1H-pyrazole-5-carboxylic acidHCID 674098312-Methoxy-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine

Produkt 1

HCID 674116535-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-methoxy-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of 2-methoxy-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine (162 mg, 0.517 mmol, prepared as described in Example 5, Step B above) in THF (10 mL) was treated with NaH (62.1 mg, 1.55 mmol, 60% dispersion in oil) at room temperature, and the mixture was allowed to stir for 1 h. Simultaneously, a solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (168 mg, 0.776 mmol, prepared as described in Example B above) in anhydrous DCM (10 mL) was treated with oxalyl chloride (67.7 μL, 0.776 mmol) and DMF (2 drops), and the mixture was stirred at room temperature for 1 h. Volatile components were removed in vacuo, and the residue was taken up in anhydrous THF (6 mL). The above-prepared acid chloride solution was added to the sodium anilide solution above, and the mixture was stirred at room temperature for 1 h. The mixture was quenched with saturated aqueous NH4Cl (20 mL) and extracted twice with EtOAc (25 mL). The residue was purified on a 12-g SEPRA Si 50 SPE column (Flow rate=15 mL/min; Eluent=EtOAc-hexanes, 1:99 for 10 min, then 1:99 to 3:17 over 40 min) to yield 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-methoxy-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide as a white solid. Mass Spectrum (LCMS, APCI pos.): Calculated for C22H21N5O4ClF3: 512.1 (M+H); Measured: 512.1.

Aufarbeitung

  1. stirringthe mixture was stirred at room temperature for 1 h
  2. customVolatile components were removed in vacuo
  3. additionThe above-prepared acid chloride solution was added to the sodium anilide solution above, and the mixture
  4. stirringwas stirred at room temperature for 1 h
  5. customThe mixture was quenched with saturated aqueous NH4Cl (20 mL)
  6. extractionextracted twice with EtOAc (25 mL)
  7. customThe residue was purified on a 12-g SEPRA Si 50 SPE column (Flow rate=15 mL/min
  8. waitEluent=EtOAc-hexanes, 1:99 for 10 min

Quellen und Nachweise

ORD-Eintrag
ord-68f0939cfa304f1592c67740cb68c933
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08680098B2

Verknüpfte Notizen

Wird geladen…