Water → 2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-N-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-benzamide

HRID 130492

Reaktionsgleichung

Reaktionsgleichung von HRID 130492
C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[N:12]1[C:16]2[C:17](=[O:28])[N:18]([C:21]3[CH:26]=[CH:25][C:24]([I:27])=[CH:23][CH:22]=3)[CH2:19][CH2:20][C:15]=2[C:14]([C:29]([F:32])([F:31])[F:30])=[N:13]1.[CH3:34][N:35]1[CH2:39][CH2:38][CH2:37][CH:36]1[CH2:40][CH2:41][NH2:42].O>C(O)CO>[I:27][C:24]1[CH:23]=[CH:22][C:21]([N:18]2[CH2:19][CH2:20][C:15]3[C:14]([C:29]([F:32])([F:30])[F:31])=[N:13][N:12]([C:5]4[CH:6]=[CH:7][C:8]([O:10][CH3:11])=[CH:9][C:4]=4[C:3]([NH:42][CH2:41][CH2:40][CH:36]4[CH2:37][CH2:38][CH2:39][N:35]4[CH3:34])=[O:2])[C:16]=3[C:17]2=[O:28])=[CH:26][CH:25]=1

Komponenten

5

Edukt 3

HCID 962WaterHCID 983882-(2-Aminoethyl)-1-methylpyrrolidineHCID 693099032-[6-(4-Iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoic acid methyl ester

Produkt 1

HCID 693137512-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-N-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-benzamideAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 174Ethylene GlycolLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

The title compound was prepared from 2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-benzoic acid methyl ester as obtained in Example 1. The ester (159 mg, 0.278 mmol) was dissolved in ethylene glycol (2 mL) containing 2-(1-methyl-pyrrolidin-2-yl)-ethylamine (400 μL, 2.78 mmol) and heated to 85° C. for 12 h. The reaction was poured into water and extracted with ethyl acetate (3×10 mL). The combined extracts were washed with water (5×10 mL), dried over sodium sulfate, filtered, and evaporated. The residue was purified by preparative thin layer chromatography to give 2-[6-(4-iodo-phenyl)-7-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-pyrazolo[3,4-c]pyridin-1-yl]-5-methoxy-N-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-benzamide (60 mg, 32%) as a faint yellow solid. MS (ES+) 668.4 (M+H)+(100%). This material (60 mg, 0.089 mmol) was combined with 2-pyridone (17 mg, 0.18 mmol), anhydrous potassium carbonate (49 mg, 0.36 mmol), copper(I) iodide (3.4 mg, 0.018 mmol), 1,10-phenanthroline (3.2 mg, 0.018 mmol), and dry-degassed dimethylsulfoxide (1.0 mL) and heated to 140° C. for 6 h. The mixture was cooled to ambient temperature and diluted with 6N ammonium hydroxide and ethyl acetate. The phases were separated, and the aqueous phase extracted once with ethyl acetate. The combined organic extracts were washed successively with water (2×) and 3N ammonium hydroxide, dried over sodium sulfate, filtered, and evaporated. The residue was purified by preparative HPLC to give the title compound as a colorless solid. MS (ES+) 635.5 (M+H)+(100%).

Aufarbeitung

  1. customas obtained in Example 1
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe combined extracts were washed with water (5×10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by preparative thin layer chromatography

Quellen und Nachweise

ORD-Eintrag
ord-9cc39669efc84ef98be2ba5802085baa
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07381732B2

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