Potassium Carbonate → 3-{4-[6-(6-Methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinolin-3-yl]-pyrazol-1-ylmethyl}-azetidine-1-carboxylic acid tert-butyl ester

HRID 655300Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 655300
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][C:13]1[N:17]3[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]3=[N:15][N:14]=1)=[CH:7][CH:6]=2.[C:23]([O:27][C:28]([N:30]1[CH2:33][CH:32]([CH2:34][N:35]2[CH:39]=[C:38](C3OC(C)(C)C(C)(C)O3)[CH:37]=[N:36]2)[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C([O-])([O-])=O.[K+].[K+].O1CCOCC1>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].O>[C:23]([O:27][C:28]([N:30]1[CH2:31][CH:32]([CH2:34][N:35]2[CH:39]=[C:38]([C:2]3[CH:3]=[N:4][C:5]4[C:10]([CH:11]=3)=[CH:9][C:8]([CH2:12][C:13]3[N:17]5[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]5=[N:15][N:14]=3)=[CH:7][CH:6]=4)[CH:37]=[N:36]2)[CH2:33]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 593202953-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinolineHCID 687083353-[4-(4,4,5,5-Tetramethyl-[1,3]dioxolan-2-yl)-pyrazol-1-ylmethyl]-azetidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 593202813-{4-[6-(6-Methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinolin-3-yl]-pyrazol-1-ylmethyl}-azetidine-1-carboxylic acid tert-butyl esterAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 53485975CID 53485975KatalysatorHCID 962WaterLösungsmittel

Versuchsvorschrift

To a microwave vessel was added 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (476 mg, 1.35 mmol, 1 equiv), 3-[4-(4,4,5,5-tetramethyl-[1,3]dioxolan-2-yl)-pyrazol-1-ylmethyl]-azetidine-1-carboxylic acid tert-butyl ester (1.2 g, 3.37 mmol, 2.5 equiv), K2CO3 (393 mg, 2.84 mmol, 2.0 equiv) followed by dioxane (12 mL) and water (6 mL). The solution was degassed with nitrogen for 10 min and then dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (44 mg, 0.06 mmol, 0.05 equiv) was added. The microwave vessel was capped and reacted in a microwave reactor at 130° C. for 30 min. The microwave vessel was cooled and then the mixture was extracted into dichloromethane and washed with water. The volatiles were removed in vacuo and the residue absorbed onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20) to obtain 3-{4-[6-(6-Methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinolin-3-yl]-pyrazol-1-ylmethyl}-azetidine-1-carboxylic acid tert-butyl ester (189 mg, 28% yield). Analytical data presented in Table 2.

Aufarbeitung

  1. customThe solution was degassed with nitrogen for 10 min
  2. customThe microwave vessel was capped
  3. customreacted in a microwave reactor at 130° C. for 30 min
  4. temperatureThe microwave vessel was cooled
  5. extractionthe mixture was extracted into dichloromethane
  6. washwashed with water
  7. customThe volatiles were removed in vacuo
  8. customthe residue absorbed onto silica gel
  9. custompurified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20)

Quellen und Nachweise

ORD-Eintrag
ord-95623009a72342c49e835e7f43839140
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071581B2

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