Hydrochloric Acid → [6-(3-Aminomethyl-4-fluoro-phenyl)-2-methoxy-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride

HRID 216131Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 216131
[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[C:15]([NH:17][CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:14]=[C:13]([O:28][CH3:29])[N:12]=2)=[CH:7][C:3]=1[CH:4]=[N:5]O.[ClH:30]>C(O)(=O)C.CCOC(C)=O.[Zn]>[ClH:30].[NH2:5][CH2:4][C:3]1[CH:7]=[C:8]([C:11]2[N:12]=[C:13]([O:28][CH3:29])[N:14]=[C:15]([NH:17][CH2:18][CH2:19][C:20]3[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=3)[CH:16]=2)[CH:9]=[CH:10][C:2]=1[F:1]

Komponenten

6

Edukt 2

HCID 313Hydrochloric AcidHCID 730190102-Fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzaldehyde oxime

Produkt 1

HCID 69064976[6-(3-Aminomethyl-4-fluoro-phenyl)-2-methoxy-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23994ZincKatalysatorHCID 176Acetic AcidLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of 2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzaldehyde oxime [860 mg, Example 26(a)] in acetic acid (10 mL) is treated with zinc powder (0.6 g, 9.2 mmol). After 1 hour at 20° C., the reaction mixture is filtered through Celite, concentrated, diluted with 1 M sodium hydroxide solution, and extracted with ethyl acetate. The extracts are dried over magnesium sulfate, filtered, and subjected to chromatography on silica gel eluting with 10% MeOH in DCM to provide the free base, which is treated with saturated HCl in EtOAc afford [6-(3-aminomethyl-4-fluoro-phenyl)-2-methoxy-pyrimidin-4-yl]-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride [720 mg, Example 27]. LCMS: RT=1.88 minutes, MS: 383 (M+H). IC50=41 nM

Aufarbeitung

  1. filtrationthe reaction mixture is filtered through Celite
  2. concentrationconcentrated
  3. additiondiluted with 1 M sodium hydroxide solution
  4. extractionextracted with ethyl acetate
  5. dry with materialThe extracts are dried over magnesium sulfate
  6. filtrationfiltered
  7. customto provide the free base, which

Quellen und Nachweise

ORD-Eintrag
ord-b0b7ab84fe0e4d688454c458def43dc3
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193183B2

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