Water → 6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-((E)-propenyl)pyrimidine-4-carboxylic acid methyl ester

HRID 506462

Reaktionsgleichung

Reaktionsgleichung von HRID 506462
[CH3:1][O:2][C:3]([C:5]1[C:10](Br)=[C:9]([NH2:12])[N:8]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([O:20][CH3:21])[C:14]=2[F:22])[N:6]=1)=[O:4].[CH:23](/B(O)O)=[CH:24]\[CH3:25].[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>[CH3:1][O:2][C:3]([C:5]1[C:10](/[CH:23]=[CH:24]/[CH3:25])=[C:9]([NH2:12])[N:8]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([O:20][CH3:21])[C:14]=2[F:22])[N:6]=1)=[O:4]

Komponenten

7

Edukt 4

HCID 962WaterHCID 25953Cesium fluorideHCID 6157276((1E)-prop-1-en-1-yl)boronic acidHCID 594321166-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid methyl ester

Produkt 1

HCID 594321216-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-((E)-propenyl)pyrimidine-4-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

6-Amino-5-bromo-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid methyl ester (400 mg, 1.02 mmol), trans-propenyl boronic acid (2132 mg, 1.54 mmol), bis(triphenylphosphine)palladium(II) dichloride (72 mg, 0.1 mmol), and cesium fluoride (311 mg, 2.05 mmol) were combined in 1,2-dimethoxyethane (2 mL) and water (2 mL) and heated at 100° C. for 15 min in a CEM microwave reactor. The cooled reaction mixture was partitioned between ethyl acetate and water; and the organic phase was dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) then purified again by reverse phase HPLC to yield the title compound: mp 133-135° C.: 1H NMR (CDCl3) δ 7.63 (m, 1H), 7.22 (m, 1H), 6.43 (m, 1H), 6.12 (m, 1H), 5.35 (br s, 2H), 3.99 (d, 3H), 3.94 (s, 3H), 1.94 (dd, 3H).

Aufarbeitung

  1. customThe cooled reaction mixture
  2. customwas partitioned between ethyl acetate and water
  3. customand the organic phase was dried
  4. concentrationconcentrated
  5. customThe product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)
  6. customthen purified again by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-51a39db33bf04cbf8bac1cf6bda2a8e4
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07786044B2

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