Cesium carbonate → 3-{2-Methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzoic acid

HRID 2110668Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2110668
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[CH:3]=1.[C:21]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1)([OH:23])=[O:22].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:28]2[CH:29]=[C:24]([CH:25]=[CH:26][CH:27]=2)[C:21]([OH:23])=[O:22])[CH:3]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[N:5]=1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 27339573-Carboxyphenylboronic acid2×HCID 57636025(6-Chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxyphenyl)-ethyl]amine2×

Produkt 1

HCID 116033013-{2-Methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzoic acidAusbeute 90,4 %

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)-[2-(4-methoxy-phenyl)-ethyl]-amine [300 mg, 1.02 mmol, Intermediate (8)], 3-carboxyphenyl boronic acid [339 mg, 2.04 mmol, Intermediate (20)], and Cs2CO3 (1.66 g, 5.1 mmol) in ethylene glycol dimethyl ether (8 mL) and water (2 mL), for a period of 5 minutes. To this mixture is added tetrakis(triphenylphosphine) palladium (0) (59 mg, 0.051 mmol) and the reaction vessel is sealed and heated to 90° C. After stirring for 17 hours the mixture is diluted with water (50 mL) and extracted with EtOAc (50 mL). The aqueous layer is acidified to pH 6 with 10% hydrochloric acid and extracted twice with EtOAc (50 mL). The organic extracts from the acidic solution are combined and dried over magnesium sulfate, filtered and concentrated to provide 3-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzoic acid [350 mg, 90.4%, Example 35(a)] as a solid. LCMS: RT=2.69 minutes, MS: 380 (M+H). 1H NMR [(CD3)2SO]: δ 8.52 (1H, s), 8.28 (3H, m), 8 (2H, m), 7.61 (2H, t, J=0.027 Hz), 7.47 (1H, m), 7.17 (2H, d, J=0.027 Hz), 6.85 (2H, d, J=0.027 Hz), 6.69 (1H, s), 3.89 (3H, s), 3.71 (3H, s), 2.8 (2H, t, J=0.024 Hz).

Aufarbeitung

  1. customthe reaction vessel is sealed
  2. extractionextracted with EtOAc (50 mL)
  3. extractionextracted twice with EtOAc (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-b008c317484d4b4d8b1f61c4963e0c7d
Quelldatensatz
uspto-grants-2009_04
Patentnummer
US07517889B2

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