Sodium hydride → 3-[2-(4,6-Dichloro-pyrimidin-5-ylamino)-pyrimidin-4-yl]-2-(4-fluoro-phenyl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

HRID 22697

Reaktionsgleichung

Reaktionsgleichung von HRID 22697
[NH2:1][C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[N:6][C:7]=1[Cl:8].[H-].[Na+].[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:26](=[O:27])[N:22]3[CH2:23][CH2:24][CH2:25][N:21]3[C:20]=2[C:28]2[CH:33]=[CH:32][N:31]=[C:30](S(C)(=O)=O)[N:29]=2)=[CH:15][CH:14]=1>C1COCC1.[NH4+].[Cl-]>[Cl:9][C:3]1[C:2]([NH:1][C:30]2[N:29]=[C:28]([C:20]3[N:21]4[CH2:25][CH2:24][CH2:23][N:22]4[C:26](=[O:27])[C:19]=3[C:16]3[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=3)[CH:33]=[CH:32][N:31]=2)=[C:7]([Cl:8])[N:6]=[CH:5][N:4]=1

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 794345-Amino-4,6-dichloropyrimidineHCID 129914052-(4-fluorophenyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

Produkt 1

HCID 99815613-[2-(4,6-Dichloro-pyrimidin-5-ylamino)-pyrimidin-4-yl]-2-(4-fluoro-phenyl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Versuchsvorschrift

To a solution of 5-amino-4,6-dichloropyrimidine (219 mg, 1.34 mmol) in THF (4 mL) is added NaH (0.07 g, 1.00 mmol). After stirring the mixture for 5 min at room temperature, 2-(4-fluorophenyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one, 5, (0.25 g, 0.67 mmol) is added to the reaction mixture. The reaction mixture is heated to reflux and stirred for 1 h. The mixture is diluted with aqueous saturated NH4Cl and extracted with twice with chloroform. The organic layers are combined, dried over MgSO4, and concentrated in vacuo to afford the crude product that is purified over silica (5% MeOH/chloroform) to provide the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) □ 8.77 (s, 1H), 8.35 (d, J=5.1 Hz, 1H), 7.35 (dd, J=9.0, 5.1 Hz, 1H), 7.10 (dd, J=8.7, 8.7 Hz, 2H), 6.71 (d, J=5.1 Hz, 1H), 4.25 (t, J=6.9 Hz, 2H), 4.12 (t, J=6.9 Hz, 2H), 2.74 (dddd, J=6.9, 6.9, 6.9, 6.9 Hz, 2H). ESI+ MS m/z (rel intensity) 458.1 (100, M++H). This compound corresponds to analog 441 from Table X.

Aufarbeitung

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux
  3. stirringstirred for 1 h
  4. extractionextracted with twice with chloroform
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto afford the crude product that
  8. customis purified over silica (5% MeOH/chloroform)

Quellen und Nachweise

ORD-Eintrag
ord-1fd63287c7cb4867850a59a44a8c6f0b
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06849627B2

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