Acetonitrile → Methyl 4-amino-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoro-3-methoxypicolinate

HRID 407238

Reaktionsgleichung

Reaktionsgleichung von HRID 407238
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15].[Cl:16][C:17]1[CH:22]=[CH:21][C:20](B2OC(C)(C)C(C)(C)O2)=[C:19]([F:32])[C:18]=1[CH:33]([F:35])[CH3:34].[F-].[K+].CC#N>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:20]2[CH:21]=[CH:22][C:17]([Cl:16])=[C:18]([CH:33]([F:35])[CH3:34])[C:19]=2[F:32])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15]

Komponenten

7

Edukt 4

HCID 6342AcetonitrileHCID 522689Potassium FluorideHCID 591269062-(4-Chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86675409Methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate

Produkt 1

HCID 71150679Methyl 4-amino-6-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-5-fluoro-3-methoxypicolinateAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel

Versuchsvorschrift

Methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (0.400 g, 1.705 mmol), 2-(4-chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (prepared as described in WO2009029735 A1 20090305; 0.671 g, 2.216 mmol), PdCl2(PPh3)2 (0.120 g, 0.170 mmol), and KF (0.258 g, 4.43 mmol) were combined in a 1:1 mixture of CH3CN (2.84 mL) and H2O (2.84 mL). The reaction mixture was irradiated in a Biotage microwave at 115° C. in a sealed vial for 20 min. The cooled reaction mixture was partitioned between EtOAc and H2O. The organic phase was dried and concentrated. The product was purified by flash chromatography (SiO2, 5-40% EtOAc in hexane gradient) to provide the title compound as a sticky brown-orange solid (0.545 g, 81%): 1H NMR (400 MHz, CDCl3) δ 7.53-7.46 (m, 1H), 7.29 (dt, J=8.4, 1.1 Hz, 1H), 6.39-6.03 (m, 1H), 4.61 (s, 2H), 3.97 (d, J=2.1 Hz, 6H), 1.85-1.68 (m, 3H); 19F NMR (376 MHz, CDCl3) δ −113.81, −113.87, −113.90, −113.95, −137.05, −137.14, −175.47, −175.52; ESIMS m/z 375 ([M+H]+), 373 ([M−H]−).

Aufarbeitung

  1. customThe reaction mixture was irradiated in a Biotage microwave at 115° C. in a sealed vial for 20 min
  2. customThe cooled reaction mixture
  3. customwas partitioned between EtOAc and H2O
  4. customThe organic phase was dried
  5. concentrationconcentrated
  6. customThe product was purified by flash chromatography (SiO2, 5-40% EtOAc in hexane gradient)

Quellen und Nachweise

ORD-Eintrag
ord-d288761e821b433fbb6d9d2dcb2c9dcb
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754229B2

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