Tetrahydrofuran → 6-Chloro-2-[[4-(2-pyrimidinyl)-1-piperazinyl]methyl]imidazo[1,2-a]pyridine

HRID 1416296

Reaktionsgleichung

Reaktionsgleichung von HRID 1416296
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([CH2:11]Cl)[N:10]=2)[CH:7]=1.Cl.Cl.[N:15]1[CH:20]=[CH:19][CH:18]=[N:17][C:16]=1[N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(N(CC)CC)C.C1COCC1>CN(C=O)C.ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([CH2:11][N:24]3[CH2:25][CH2:26][N:21]([C:16]4[N:15]=[CH:20][CH:19]=[CH:18][N:17]=4)[CH2:22][CH2:23]3)[N:10]=2)[CH:7]=1

Komponenten

7

Edukt 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 48683896-Chloro-2-(chloromethyl)imidazo[1,2-a]pyridineHCID 116802722-Piperazinylpyrimidine dihydrochloride

Produkt 1

HCID 193671546-Chloro-2-[[4-(2-pyrimidinyl)-1-piperazinyl]methyl]imidazo[1,2-a]pyridineAusbeute 41,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 6-chloro-2-(chloromethyl)imidazo[1,2-a]pyridine (Example 4, Step 1; 0.335 g), 1-(pyrimidin-2-yl)piperazine dihydrochloride (Aldrich; 0.395 g), triethylamine (Aldrich; 0.522 g), THF (5 mL), and dichloromethane (5 mL) is heated at 80° C. for 45 min and then at 60° C. for 5 h, at which time DMF (1 mL) is added. After stirring for a total of 10.5 h, the mixture is allowed to cool and stir at room temperature for an additional 12 h. The solvents are then removed under reduced pressure and the residue is partitioned between dichloromethane and aq. sodium bicarbonate. The organic layers are dried over sodium sulfate and concentrated. The residue is chromatographed on silica gel using methanol/dichloromethane (4/96) and the appropriate fractions are combined and concentrated to give 0.228 g of the title compound. Crystallization from methanol-dichloromethane-hexane gives 0.315 g of the title compound in two crops; mp 114-115° C.; MS m/z 328, 330; IR (mineral oil) 1481, 1357, 1584, 1439, 1253, 1548 cm-1. 1H NMR (CDCl3) δ2.64, 3.76, 3.87, 6.48, 7.12, 7.52, 7.54, 8.14, 8.30.

Aufarbeitung

  1. temperatureto cool
  2. stirringstir at room temperature for an additional 12 h
  3. customThe solvents are then removed under reduced pressure
  4. customthe residue is partitioned between dichloromethane and aq. sodium bicarbonate
  5. dry with materialThe organic layers are dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-afe51ed84064436283dfe65042de8419
Quelldatensatz
uspto-grants-1999_06
Patentnummer
US05912246

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