Diethyl Ether → N-cyclopentyl-4-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine

HRID 1797068Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1797068
CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:8]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)=[N:9][N:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=12)=O.Cl.[CH:29]1([NH:34][C:35]([NH2:37])=[NH:36])[CH2:33][CH2:32][CH2:31][CH2:30]1.C(=O)([O-])[O-].[K+].[K+].CCOCC>CN1CCCC1=O.O>[CH:29]1([NH:34][C:35]2[N:37]=[C:5]([C:7]3[C:8]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)=[N:9][N:10]4[CH:15]=[C:14]([C:16]([F:18])([F:17])[F:19])[CH:13]=[CH:12][C:11]=34)[CH:4]=[CH:3][N:36]=2)[CH2:33][CH2:32][CH2:31][CH2:30]1

Komponenten

7

Edukt 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 11501715(2E)-3-(dimethylamino)-1-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-propen-1-oneHCID 178479367HCID 178479367, Verbindung

Produkt 1

HCID 22174839N-cyclopentyl-4-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamineAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

To a solution of (2E)-3-(dimethylamino)-1-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-propen-1-one (314 mg, 0.83 mmol)) in 1-methyl-2-pyrrolidinone (3 mL) was added N-cyclopentylguanidine hydrochloride (271 mg, 1.66 mmol) and potassium carbonate (229 mg, 1.66 mmol). The mixture was heated at 140° C. for 8 hours. Upon cooling to room temperature, ether was added followed by water. The organics were washed with brine, and the aqueous layer was extracted with ether. The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica (4:1 hexanes-ethyl acetate) to give N-cyclopentyl-4-[2-(4-fluorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine (204 mg, 56%) as a white solid. 1 H NMR (CDCl3): δ 8.84 (s, 1 H), 8.51 (d, 1 H), 8.11 (d, 1 H), 7.64 (dd, 2 H), 7.44 (dd, 1 H), 7.17 (t, 2 H), 6.33 (d, 1H), 5.17 (d, 1H), 4.34 (m, 1H), 2.15–2.06 (m, 2 H), 1.84–1.52 (m, 6 H); 19F NMR (CDCl3): δ −62.70, −112.25; MS m/z 442 (M+1); mp 155–156° C.

Aufarbeitung

  1. temperatureUpon cooling to room temperature
  2. washThe organics were washed with brine
  3. extractionthe aqueous layer was extracted with ether
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica (4:1 hexanes-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-6aff180aee6144338b6520bc928834c2
Quelldatensatz
uspto-grants-2006_04
Patentnummer
US07034030B2

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