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

HRID 1191234Notes

Reaction equation

HRID 1191234 reaction equation
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2[N:12]([CH3:21])[N:13]=[C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:15]=2[Cl:16])=[O:10])[C:5]([N+:22]([O-:24])=[O:23])=[CH:4][CH:3]=1.[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>COCCOC.O>[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2[N:12]([CH3:21])[N:13]=[C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:15]=2[Cl:16])=[O:10])[C:5]([N+:22]([O-:24])=[O:23])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27343222-Chlorophenylboronic acidHCID 866574255-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide

Product 1

HCID 674124515-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [6-(2-chloro-phenyl)-3-nitro-pyridin-2-yl]-amide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide (200 mg, 0.480 mmol, prepared as described in the previous step) in DME (20 mL) and water (5 mL) was treated with 2-chlorophenylboronic acid (78.8 mg, 0.504 mmol) and cesium carbonate (469 mg, 1.44 mmol). The resulting mixture was degassed via sonication, placed under Ar, treated with PdCl2(dppf).DCM (19.6 mg, 0.0240 mmol), and heated to 90° C. for 3 h. The cooled mixture was then diluted with water (40 mL) and extracted twice with EtOAc (50 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 24-g SEPRA Si 50 SPE column (Isco system: Flow rate=20 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 10 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-(2-chloro-phenyl)-3-nitro-pyridin-2-yl]-amide as a yellow solid. Mass Spectrum (LCMS, APCI pos.): Calculated for C20H19Cl2N5O3: 448.1 (M+H); Measured: 448.0.

Workup

  1. customThe resulting mixture was degassed via sonication
  2. additiontreated with PdCl2(dppf)
  3. extractionextracted twice with EtOAc (50 mL)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 24-g SEPRA Si 50 SPE column (Isco system

Sources & evidence

ORD record
ord-47e5444be3154149bd1eb547cf9e24da
Source dataset
uspto-grants-2014_03
Patent number
US08680098B2

Reaction notes

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