Cesium carbonate → 2-(3-{2-Methoxy-6-[(thiophen-3-ylmethyl)-amino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid

HRID 2110741Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2110741
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][C:12]2[CH:16]=[CH:15][S:14][CH:13]=2)[CH:3]=1.[C:17]([C:20]([C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1)([CH3:22])[CH3:21])([OH:19])=[O:18].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:9][O:8][C:6]1[N:7]=[C:2]([C:25]2[CH:24]=[C:23]([C:20]([CH3:22])([CH3:21])[C:17]([OH:19])=[O:18])[CH:28]=[CH:27][CH:26]=2)[CH:3]=[C:4]([NH:10][CH2:11][C:12]2[CH:16]=[CH:15][S:14][CH:13]=2)[N:5]=1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 86615704(6-Chloro-2-methoxy-pyrimidin-4-yl)-thiophen-3-ylmethyl-amine

Produkt 1

HCID 116106622-(3-{2-Methoxy-6-[(thiophen-3-ylmethyl)-amino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acidAusbeute 4,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 962WaterLösungsmittel2×HCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Argon is bubbled through a mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-thiophen-3-ylmethyl-amine (216 mg, 0.84 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl boronic acid [312 mg, 1.5 mmol, see Example 49(b) step 2], Cs2CO3 (821 mg, 2.52 mmol), and tetrakis(triphenylphosphine) palladium (0) (92 mg, 0.08 mmol) in ethylene glycol dimethyl ether (2.5 mL) and water (0.5 mL), for a period of 10 minutes. The reaction vessel is sealed and heated to 90° C. After stirring for 6 hours the heating is turned off and the mixture is allowed to cool to ambient temperature upon standing for 24 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 concentrated to afford 2-(3-{2-methoxy-6-[(thiophen-3-ylmethyl)-amino]-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [15 mg, 4.6%, Example 71] as a solid. LCMS RT=1.94 minutes, MS: 384 (M+H). IC50=393 nM

Aufarbeitung

  1. customThe reaction vessel is sealed
  2. temperatureto cool to ambient temperature
  3. waitupon standing for 24 hours
  4. extractionextracted twice with EtOAc (25 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-9d202bd06a024ff9b3f1d55f9cdf3c94
Quelldatensatz
uspto-grants-2009_04
Patentnummer
US07517889B2

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