Sodium Bicarbonate → Methyl 3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-3-methylbiphenyl-4-carboxylate

HRID 2356801

Reaktionsgleichung

Reaktionsgleichung von HRID 2356801
B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.Br[C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([CH3:30])[CH:21]=1.CC([O-])=O.[K+].Br[C:37]1[CH:42]=[CH:41][C:40]([NH:43][C:44]2[S:45][C:46]3[CH:52]=[C:51]([F:53])[CH:50]=[CH:49][C:47]=3[N:48]=2)=[C:39]([F:54])[CH:38]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[F:54][C:39]1[CH:38]=[C:37]([C:20]2[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([CH3:30])[CH:21]=2)[CH:42]=[CH:41][C:40]=1[NH:43][C:44]1[S:45][C:46]2[CH:52]=[C:51]([F:53])[CH:50]=[CH:49][C:47]=2[N:48]=1

Komponenten

9

Edukt 5

HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 7147089N-(4-bromo-2-fluorophenyl)-6-fluoro-1,3-benzothiazol-2-amineHCID 22031226Methyl 4-bromo-2-methylbenzoate

Produkt 1

HCID 59385264Methyl 3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-3-methylbiphenyl-4-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

As shown in Reaction Scheme 6, a mixture of bis(pinacolato)diboron (0.55 g, 2.2 mmol), methyl 4-bromo-2-methylbenzoate (0.50 g, 2.2 mmol), palladium(II) acetate (0.01 g, 0.07 mmol), and KOAc (0.64 g, 6.6 mmol) in DMF (7.5 mL) was degassed with argon for 30 min at rt. The mixture was then heated at 80° C. for 4 h. After cooling the mixture to rt, N-(4-bromo-2-fluorophenyl)-6-fluoro-1,3-benzothiazol-2-amine (0.74 g, 2.2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.08 g, 0.07 mmol), and saturated aqueous NaHCO3 (5 mL) were added. The mixture was heated at 85° C. overnight. The mixture was poured into ice water and extracted with EtOAc. The combined organic phases were dried over Na2SO4, concentrated in vacuo, and purified by column chromatography (20% EtOAc in hexanes). This yielded 0.345 g (39%) of the title compound. LC/MS m/z 411.3 (MH+; retention time 4.15 min. 1H NMR (400 MHz, CD2Cl2) 2.62 (s, 3H), 3.90 (s, 3H), 7.10 (t, 1H), 7.39-7.53 (m, 5H), 7.62-7.70 (m, 1H), 7.99 (d, 1H), 8.58 (t, 1H).

Aufarbeitung

  1. customAs shown in Reaction Scheme 6
  2. customwas degassed with argon for 30 min at rt
  3. temperatureAfter cooling the mixture to rt
  4. temperatureThe mixture was heated at 85° C. overnight
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organic phases were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography (20% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-a365d6159022483cb4e59b5445641195
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07759376B2

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