Hydrochloric Acid → 1-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-cyclopentanecarboxylic acid

HRID 216220

Reaktionsgleichung

Reaktionsgleichung von HRID 216220
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]([Cl:19])=[CH:15][C:14]=2[Cl:20])[CH:3]=1.[C:21]([C:24]1([C:29]2[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=2)[CH2:28][CH2:27][CH2:26][CH2:25]1)([OH:23])=[O:22].C([O-])([O-])=O.[Cs+].[Cs+].Cl>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:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[CH2:12][CH2:11][NH:10][C:4]1[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:31]2[CH:30]=[C:29]([C:24]3([C:21]([OH:23])=[O:22])[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH:34]=[CH:33][CH:32]=2)[CH:3]=1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 576360046-Chloro-N-[2-(2,4-dichlorophenyl)ethyl]-2-methoxy-4-pyrimidinamineHCID 690700543-(1-Carboxy-cyclopentyl)-phenylboronic acid

Produkt 1

HCID 533165751-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-cyclopentanecarboxylic acid

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-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine [330 mg, 0.99 mmol], 3-(1-carboxy-cyclopentyl)-phenylboronic acid [580 mg, 2.48 mmol] and Cs2CO3 (808 mg, 2.48 mmol) in ethylene glycol dimethyl ether (4 mL) and water (1 mL), for a period of 5 minutes. To this mixture is added tetrakis(triphenylphosphine)palladium (0) (116 mg, 0.1 mmol) and the reaction vessel is sealed and heated to 90° C. After stirring for 8 hours the mixture is diluted with water (30 mL) acidified to pH 1 with concentrated HCl and extracted thrice with EtOAc (30 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and concentrated to afford 1-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-cyclopentanecarboxylic acid as a solid that is treated with HCl in ethyl acetate. The material is then dissolved in acetone (5 mL) and heptane (15 mL) is added and allowed to stand at ambient temperature for 16 hours. The solvent is decanted from the crystals and dried under high vacuum to provide 1-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-cyclopentanecarboxylic acid hydrochloride [48 mg, 9%, Example 74] as a solid. LCMS RT=2.54 minutes, MS: 486 (M+H). IC50=0.5 nM

Aufarbeitung

  1. customthe reaction vessel is sealed
  2. extractionextracted thrice with EtOAc (30 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-24c38159a20848f488008dc9a69c1415
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193183B2

Verknüpfte Notizen

Wird geladen…