Cesium fluoride → 6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-methoxypyrimidine-4-carboxylic acid methyl ester

HRID 1988543Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1988543
[CH3:1][O:2][C:3]([C:5]1[C:10]([O:11][CH3:12])=[C:9]([NH2:13])[N:8]=[C:7](Cl)[N:6]=1)=[O:4].[Cl:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[C:18]([F:25])[C:17]=1[O:26][CH3:27].[F-].[Cs+]>COCCOC.O.C(OCC)(=O)C.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>[CH3:1][O:2][C:3]([C:5]1[C:10]([O:11][CH3:12])=[C:9]([NH2:13])[N:8]=[C:7]([C:19]2[CH:20]=[CH:21][C:16]([Cl:15])=[C:17]([O:26][CH3:27])[C:18]=2[F:25])[N:6]=1)=[O:4]

Komponenten

8

Edukt 3

HCID 25953Cesium fluorideHCID 441297064-Chloro-2-fluoro-3-methoxyphenylboronic acidHCID 52270701Methyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate

Produkt 1

HCID 591269286-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-methoxypyrimidine-4-carboxylic acid methyl esterAusbeute 52,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

6-Amino-2-chloro-5-methoxypyrimidine-4-carboxylic acid methyl ester (0.2 g, 0.9 mmol), 4-chloro-2-fluoro-3-methoxyphenylboronic acid (0.29 g, 1.4 mmol), bis(triphenylphosphine)palladium(II) dichloride (65 mg, 0.1 mmol), and cesium fluoride (0.28 g, 1.9 mmol) were combined in 1 mL of 1,2-dimethoxyethane and 1 mL of water. The reaction mixture was heated in a CEM microwave at 100° C. for 15 min (other temperature/time pairs used in the subsequent examples were 110° C. for 15 min and 150° C. for 5 min). The cooled reaction mixture was diluted with ethyl acetate, washed with water, washed with brine, dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) to yield the title compound (162 mg, 51.1% yield): mp 155-158° C.; 1H NMR (CDCl3): δ 7.58 (dd, 1H), 7.20 (dd, 1H), 5.56 (br s, 2H) 4.00 (s, 3H), 3.99 (d, 3H), 3.94 (s, 3H).

Aufarbeitung

  1. customThe cooled reaction mixture
  2. washwashed with water
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)

Quellen und Nachweise

ORD-Eintrag
ord-9902130fed2c4a46bf5f65f8b434dfa3
Quelldatensatz
uspto-grants-2010_01
Patentnummer
US07642220B2

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