Sodium Carbonate → Ethyl 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]nicotinate

HRID 1986863

Reaktionsgleichung

Reaktionsgleichung von HRID 1986863
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].I[C:37]1[CH:38]=[N:39][N:40]2[CH:45]=[C:44]([C:46]3[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=3)[CH:43]=[N:42][C:41]=12.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[CH3:53][O:52][C:49]1[CH:48]=[CH:47][C:46]([C:44]2[CH:43]=[N:42][C:41]3[N:40]([N:39]=[CH:38][C:37]=3[C:2]3[CH:3]=[N:4][CH:5]=[C:6]([CH:12]=3)[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:45]=2)=[CH:51][CH:50]=1

Komponenten

11

Edukt 5

HCID 10340Sodium CarbonateHCID 140785Ethyl 5-bromopyridine-3-carboxylateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 577226133-Iodo-6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine

Produkt 1

HCID 57722617Ethyl 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]nicotinate

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24290Palladium ChlorideKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of ethyl 5-bromonicotinate (500 mg, 2.17 mmol, 1 equiv), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (662 mg, 2.61 mmol, 1.20 equiv), potassium acetate (639 g, 6.51 mmol, 3.00 equiv), and 1,1′-bis (diphenylphophino)-ferrocene)dichloropalladium (89 mg, 0.11 mmol, 0.050 equiv) in DMF (5 mL) was heated at 80° C. for 16 hours. The mixture was partitioned between water (100 mL) and ethyl acetate (2×50 mL). The organic layer was dried over sodium sulfate and concentrated. A solution of the residue, 3-iodo-6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine (2-1, 254 mg, 0.723 mmol, 0.333 equiv), tetrakis(triphenylphosphine)palladium (50 mg, 0.043 mmol, 0.020 equiv) in a mixture of aqueous 2M sodium carbonate solution (1 mL) and dioxane (10 mL) was heated at reflux for 16 hours. The reaction was then partitioned between water (50 mL) and ethyl acetate (2×50 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was suspended in methanol and filtered to give ethyl 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]nicotinate (2-2) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 9.50 (d, 1H, J=2.2 Hz), 9.12 (d, 1H, J=2.2 Hz), 8.96 (t, 1H, J=2.2 Hz), 8.88 (d, 1H, J=2.2 Hz), 8.8.3 (d, 1H, J=2.4 Hz), 8.54 (s, 1H), 7.56 (d, 2H, J=8.8 Hz), 7.08 (d, 2H, J=8.8 Hz), 4.48 (q, 2H, J=7.3 Hz), 3.90 (s, 3H), 1.46 (t, 3H, J=7.1 Hz).

Aufarbeitung

  1. customThe mixture was partitioned between water (100 mL) and ethyl acetate (2×50 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. temperaturewas heated
  5. temperatureat reflux for 16 hours
  6. customThe reaction was then partitioned between water (50 mL) and ethyl acetate (2×50 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. concentrationconcentrated
  9. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-1d2fc3dece8f447082dd2df7c01c5557
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07550470B2

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