Sodium Carbonate → 5-(2-(4-Fluorophenyl)thiazol-4-yl)-3-methoxypyridin-2-amine

HRID 538427

Reaktionsgleichung

Reaktionsgleichung von HRID 538427
Br[C:2]1[N:3]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[S:5][CH:6]=1.[CH3:14][O:15][C:16]1[C:17]([NH2:31])=[N:18][CH:19]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:21]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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:13][C:10]1[CH:11]=[CH:12][C:7]([C:4]2[S:5][CH:6]=[C:2]([C:20]3[CH:21]=[C:16]([O:15][CH3:14])[C:17]([NH2:31])=[N:18][CH:19]=3)[N:3]=2)=[CH:8][CH:9]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 457882314-Bromo-2-(4-fluorophenyl)thiazoleHCID 533980593-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

Produkt 1

HCID 665909545-(2-(4-Fluorophenyl)thiazol-4-yl)-3-methoxypyridin-2-amineAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A mixture of 4-bromo-2-(4-fluorophenyl)thiazole (450 mg, 1.7 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (400 mg, 1.6 mmol), and aqueous 2.0 M Na2CO3 solution (2.3 mL, 4.6 mmol) in DME (6.8 mL) was sparged with Ar for 3 min. Tetrakis(triphenylphosphine)palladium(0) (120 mg, 0.1 mmol) was added and the reaction mixture was sparged with Ar for 1 min. The reaction was sealed and irradiated at 115° C. for 25 min in a microwave reactor. The reaction mixture was partitioned with EtOAc (50 mL) and saturated aqueous NaHCO3 solution (100 mL). The separated organic layer was washed with saturated aqueous NaHCO3 solution (50 mL). The organic layer was extracted with aqueous 0.5 N HCl solution (2×25 mL). The combined acidic aqueous portions were washed with EtOAc (30 mL), neutralized with saturated aqueous NaHCO3 solution and extracted with EtOAc (3×50 mL). The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by column chromatography over silica gel (SiO2, 100% EtOAc) to furnish 145 mg (88% purity) of 5-(2-(4-fluorophenyl)thiazol-4-yl)-3-methoxypyridin-2-amine which was directly used in the next step: LCMS (m/z): 302.1 (MH+), tR=0.75 min.

Aufarbeitung

  1. customwas sparged with Ar for 3 min
  2. customthe reaction mixture was sparged with Ar for 1 min
  3. customThe reaction was sealed
  4. customirradiated at 115° C. for 25 min in a microwave reactor
  5. customThe reaction mixture was partitioned with EtOAc (50 mL) and saturated aqueous NaHCO3 solution (100 mL)
  6. washThe separated organic layer was washed with saturated aqueous NaHCO3 solution (50 mL)
  7. extractionThe organic layer was extracted with aqueous 0.5 N HCl solution (2×25 mL)
  8. washThe combined acidic aqueous portions were washed with EtOAc (30 mL)
  9. extractionextracted with EtOAc (3×50 mL)
  10. dry with materialThe organic layer was dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude material was purified by column chromatography over silica gel (SiO2, 100% EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-bc56b03da8174e6d8666aa9ade278ac7
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865732B2

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