Sodium Carbonate → methyl 5-(7-((1S,2S)-2-fluorocyclopropanecarboxamido)-2,6-naphthyridin-3-yl)-4-methylpicolinate

HRID 468941Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 468941
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([C@@H:15]3[CH2:17][C@@H:16]3[F:18])=[O:14])[N:8]=[CH:9]2)=[CH:4][N:3]=1.[CH3:19][C:20]1[C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][N:23]=[C:22]([C:35]([O:37][CH3:38])=[O:36])[CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:18][C@H:16]1[CH2:17][C@H:15]1[C:13]([NH:12][C:7]1[CH:6]=[C:5]2[C:10]([CH:11]=[C:2]([C:25]3[C:20]([CH3:19])=[CH:21][C:22]([C:35]([O:37][CH3:38])=[O:36])=[N:23][CH:24]=3)[N:3]=[CH:4]2)=[CH:9][N:8]=1)=[O:14]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 67977255Methyl 4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylateHCID 86674973(1S,2S)-N-(7-chloro-2,6-naphthyridin-3-yl)-2-fluorocyclopropanecarboxamide

Produkt 1

HCID 71115323methyl 5-(7-((1S,2S)-2-fluorocyclopropanecarboxamido)-2,6-naphthyridin-3-yl)-4-methylpicolinateAusbeute 52,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)KatalysatorHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A mixture of (1S,2S)—N-(7-chloro-2,6-naphthyridin-3-yl)-2-fluorocyclopropanecarboxamide (100 mg, 0.376 mmol), methyl 4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinate (156 mg, 0.565 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (26.6 mg, 0.038 mmol) and saturated aqueous sodium carbonate solution (0.1 mL) in acetonitrile (1 mL) was heated under microwave irradiation (Biotage) at 130° C. for 30 minutes. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (20 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by flash chromatography (4 g, Silica, 0-100% ethyl acetate in heptane). Desired fractions were combined and evaporated in vacuo to afford the title compound as a pale yellow solid (75 mg, 52%), which was used in the next step without further purification.

Aufarbeitung

  1. washwashed with water (20 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by flash chromatography (4 g, Silica, 0-100% ethyl acetate in heptane)
  8. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-389fa59d88cb47d2b32068322ffc971a
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623889B2

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