Sodium hydride → 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-(4-methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide

HRID 570263

반응식

HRID 570263 반응식
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[C:13]([N+:14]([O-:16])=[O:15])=[C:12]([NH2:17])[CH:11]=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:26])[F:25])[N:9]=2)[CH2:4][CH2:3]1.[H-].[Na+].[C:30]([C:34]1[C:35]([Cl:43])=[C:36]([C:40](O)=[O:41])[N:37]([CH3:39])[N:38]=1)([CH3:33])([CH3:32])[CH3:31].C(Cl)(=O)C(Cl)=O>C1COCC1.C(Cl)Cl.CN(C=O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[C:13]([N+:14]([O-:16])=[O:15])=[C:12]([NH:17][C:40]([C:36]3[N:37]([CH3:39])[N:38]=[C:34]([C:30]([CH3:32])([CH3:31])[CH3:33])[C:35]=3[Cl:43])=[O:41])[CH:11]=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]([F:27])([F:25])[F:26])[N:9]=2)[CH2:4][CH2:3]1

참가 물질

8

반응물 4

HCID 24758Sodium hydrideHCID 65578Oxalyl chlorideHCID 584254493-tert-butyl-4-chloro-1-methyl-1H-pyrazole-5-carboxylic acidHCID 674108042-(4-Methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine

생성물 1

HCID 674111645-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-(4-methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 2-(4-methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine (240 mg, 0.630 mmol, prepared as described in the previous step) in THF (10 mL) was treated with NaH (75.6 mg, 1.89 mmol, 60% dispersion in mineral oil) at room temperature for 1 h. At the same time, a solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (164 mg, 0.756 mmol, prepared as described in Example B) in DCM (10 mL) was treated with oxalyl chloride (66.0 μL, 0.756 mmol) and DMF (2 drops) at room temperature for 1 h. The resulting mixture was concentrated in vacuo, taken up in THF (6 mL), and added to the sodium anilide solution at room temperature. The solution was stirred at room temperature for 30 min, quenched with saturated aqueous NH4Cl (20 mL), and extracted three times with EtOAc (25 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=15 mL/min; Eluent=EtOAc-hexanes, 3:2 v/v for 5 min, then 3:2 to 4:1 v/v over 40 min) to yield 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-(4-methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide as an orange solid. Mass Spectrum (LCMS, APCI pos.): Calculated for C26H29ClF3N7O3: 580.2 (M+H); Measured: 580.2.

후처리

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. additionadded to the sodium anilide solution at room temperature
  3. customquenched with saturated aqueous NH4Cl (20 mL)
  4. extractionextracted three times with EtOAc (25 mL)
  5. dry with materialThe combined extracts were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on a 24-g SEPRA Si 50 SPE column (Isco system
  8. waitEluent=EtOAc-hexanes, 3:2 v/v for 5 min

출처 및 근거

ORD 기록
ord-8da0f52e4a2244989518124a097248d4
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09023846B2

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