Sodium hydride → 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide

HRID 570250

Reaktionsgleichung

Reaktionsgleichung von HRID 570250
[Br:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1.[H-].[Na+].[C:14]([C:18]1[C:19]([Cl:27])=[C:20]([C:24](O)=[O:25])[N:21]([CH3:23])[N:22]=1)([CH3:17])([CH3:16])[CH3:15].C(Cl)(=O)C(Cl)=O>C1COCC1.C(Cl)Cl.CN(C=O)C>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:24]([C:20]2[N:21]([CH3:23])[N:22]=[C:18]([C:14]([CH3:16])([CH3:15])[CH3:17])[C:19]=2[Cl:27])=[O:25])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1

Komponenten

8

Edukt 4

HCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 120977456-Bromo-3-nitro-2-pyridinamineHCID 584254493-tert-butyl-4-chloro-1-methyl-1H-pyrazole-5-carboxylic acid

Produkt 1

HCID 866574255-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of 6-bromo-3-nitro-pyridin-2-ylamine (750 mg, 3.44 mmol) in THF (20 mL) was treated with NaH (413 mg, 10.3 mmol) at room temperature for 1 h. Simultaneously a solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (969 mg, 4.47 mmol, prepared as described in Example B) in DCM (20 mL) was treated with oxalyl chloride (390 μL, 4.47 mmol) and DMF (4 drops) at room temperature for 1 h. The acid chloride solution was concentrated to dryness in vacuo, taken up in THF (10 mL), and added to the sodium anilide solution. The resulting mixture was stirred at room temperature for 15 min, quenched with saturated aqueous NH4Cl (50 mL), and extracted twice with EtOAc (60 mL, 20 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 40-g SEPRA Si 50 SPE column (Isco system: Flow rate=25 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 1 min, then 1:99 to 3:17 v/v over 40 min) to yield 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide as a pale yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 10.48 (br. s., 1H), 8.31 (d, J=8.6 Hz, 1H), 7.46 (d, J=8.6 Hz, 1H), 4.12 (s, 3H), 1.42 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C14H15BrClN5O3: 416.0 (M+H); Measured: 416.1.

Aufarbeitung

  1. concentrationThe acid chloride solution was concentrated to dryness in vacuo
  2. additionadded to the sodium anilide solution
  3. customquenched with saturated aqueous NH4Cl (50 mL)
  4. extractionextracted twice with EtOAc (60 mL, 20 mL)
  5. dry with materialThe combined extracts were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on a 40-g SEPRA Si 50 SPE column (Isco system
  8. waitEluent=EtOAc/hexanes, 1:99 v/v for 1 min

Quellen und Nachweise

ORD-Eintrag
ord-b6cde6d17f794141b53e3f23a0c3c437
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09023846B2

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