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

HRID 1191236노트

반응식

HRID 1191236 반응식
[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:17])([F:16])[F:15])[N:5]=[C:4]([NH2:18])[C:3]=1[N+:19]([O-:21])=[O:20].[H-].[Na+].[C:24]([C:28]1[CH:29]=[C:30]([C:34](Cl)=[O:35])[N:31]([CH3:33])[N:32]=1)([CH3:27])([CH3:26])[CH3:25]>C1COCC1>[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:15])([F:16])[F:17])[N:5]=[C:4]([NH:18][C:34]([C:30]2[N:31]([CH3:33])[N:32]=[C:28]([C:24]([CH3:26])([CH3:25])[CH3:27])[CH:29]=2)=[O:35])[C:3]=1[N+:19]([O-:21])=[O:20]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 27356843-(Tert-Butyl)-1-Methyl-1H-Pyrazole-5-Carbonyl ChlorideHCID 674097756-Methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-ylamine

생성물 1

HCID 674115755-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [6-methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of 6-methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-ylamine (150 mg, 0.503 mmol, prepared as described in Example 2, STEP A) in THF (10 mL) was treated with NaH (60.4 mg, 1.51 mmol, 60% dispersion in oil), and the resulting mixture was allowed to stir for 30 min at room temperature. 5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl chloride (131 mg, 0.654 mmol) was added as a solution in THF (3 mL). After 15 min, the mixture was quenched with saturated aqueous NH4Cl (20 mL) and extracted twice with EtOAc (25 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 12-g SEPRA Si 50 SPE column (Isco system: Flow rate=15 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 10 min, then 1:99 to 1:4 v/v over 40 min) to yield 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid [6-methyl-5-nitro-2-(2-trifluoromethyl-phenyl)-pyrimidin-4-yl]-amide as a colorless glassy solid. 1H-NMR (400 MHz, CDCl3) δ: 9.10 (s, 1H), 7.79-7.86 (m, 2H), 7.60-7.72 (m, 2H), 6.64 (s, 1H), 4.14 (s, 3H), 2.83 (s, 3H), 1.33 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C21H21F3N6O3: 463.2 (M+H); Measured: 463.2.

후처리

  1. waitAfter 15 min
  2. customthe mixture was quenched with saturated aqueous NH4Cl (20 mL)
  3. extractionextracted twice with EtOAc (25 mL)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 12-g SEPRA Si 50 SPE column (Isco system
  7. waitEluent=EtOAc/hexanes, 1:99 v/v for 10 min

출처 및 근거

ORD 기록
ord-d7f8309c84704beaa6298ee7723ee3f6
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680098B2

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