Water → 2-Chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-(difluoromethoxy)pyridin-4-amine

HRID 407219

Reaktionsgleichung

Reaktionsgleichung von HRID 407219
Br[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([O:9][CH:10]([F:12])[F:11])=[C:4]([NH2:13])[CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B2OCCCO2)=[C:17]([F:27])[C:16]=1[O:28][CH3:29].[F-].[Cs+].O>COCCOC.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>[Cl:8][C:6]1[C:5]([O:9][CH:10]([F:12])[F:11])=[C:4]([NH2:13])[CH:3]=[C:2]([C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[C:16]([O:28][CH3:29])[C:17]=2[F:27])[N:7]=1

Komponenten

7

Edukt 4

HCID 962WaterHCID 25953Cesium fluorideHCID 577824192-(4-Chloro-2-fluoro-3-methoxyphenyl)-1,3,2-dioxaborinaneHCID 866754046-Bromo-2-chloro-3-(difluoromethoxy)pyridin-4-amine

Produkt 1

HCID 866754052-Chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-3-(difluoromethoxy)pyridin-4-amineAusbeute 84,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

6-Bromo-2-chloro-3-(difluoromethoxy)pyridin-4-amine (368 mg, 1.346 mmol), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-1,3,2-dioxaborinane (395 mg, 1.615 mmol), PdCl2(PPh3)2 (47.2 mg, 0.067 mmol), and CsF (409 mg, 2.69 mmol) were combined in DME (2 mL) and H2O (2 mL) and heated in a Biotage microwave reactor at 110° C. for 15 min. The cooled reaction mixture was partitioned between EtOAc and H2O. The organic phase was dried, concentrated onto silica gel, and purified by flash chromatography (SiO2, EtOAc/hexane gradient). This process yielded the title compound as a white solid (0.4 g, 84%): mp 152-154° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.63-7.50 (m, 1H), 7.42 (dd, J=8.7, 1.6, 1H), 7.16 (d, J=1.8, 1H), 7.02 (t, J=73.4, 1H), 6.70 (s, 2H), 3.93 (d, J=0.8, 3H); ESIMS m/z 354 ([M+H]+), 352 ([M−H]−).

Aufarbeitung

  1. customThe cooled reaction mixture
  2. customwas partitioned between EtOAc and H2O
  3. customThe organic phase was dried
  4. concentrationconcentrated onto silica gel
  5. custompurified by flash chromatography (SiO2, EtOAc/hexane gradient)

Quellen und Nachweise

ORD-Eintrag
ord-67c9ae402d9048d795b7fd9de05e6325
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754229B2

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