Cesium carbonate → 2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxymethyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid

HRID 216239Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 216239
Cl[C:2]1[N:7]=[C:6]([CH2:8][O:9][CH3:10])[N:5]=[C:4]([NH:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[Cl:21])[CH:3]=1.[C:22]([C:25]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)([CH3:27])[CH3:26])([OH:24])=[O:23].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:21][C:15]1[CH:16]=[C:17]([Cl:20])[CH:18]=[CH:19][C:14]=1[CH2:13][CH2:12][NH:11][C:4]1[N:5]=[C:6]([CH2:8][O:9][CH3:10])[N:7]=[C:2]([C:30]2[CH:29]=[C:28]([C:25]([CH3:27])([CH3:26])[C:22]([OH:24])=[O:23])[CH:33]=[CH:32][CH:31]=2)[CH:3]=1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 86615707(6-Chloro-2-methoxymethyl-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine

Produkt 1

HCID 533231512-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxymethyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acidAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×HCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Argon is bubbled through a mixture of (6-chloro-2-methoxymethyl-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine (200 mg, 0.58 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl boronic acid [266 mg, 1.28 mmol, see Example 49(b) step 2], Cs2CO3 (1.56 g, 2.52 mmol), and tetrakis(triphenylphosphine)palladium (0) (69 mg, 0.06 mmol) in ethylene glycol dimethyl ether (4 mL) and water (1 mL), for a period of 10 minutes. The reaction vessel is sealed and heated to 90° C. After stirring for 16 hours the mixture is diluted with water (40 mL) and extracted twice with EtOAc (25 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and evaporated. The residue is subjected to chromatography on silica gel eluting with 40% ethyl acetate:heptane to afford 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxymethyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [165 mg, 60%, Example 85] as a solid. LCMS RT=2.59 minutes, MS: 474 (M+H). IC50=2.7 nM

Aufarbeitung

  1. customThe reaction vessel is sealed
  2. extractionextracted twice with EtOAc (25 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-e1f471b2979744889523985c76f8243e
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193183B2

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