Trifluoroacetic acid → 1-(2,5-Dichloro-pyrimidin-4-yl)-piperidine-4-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide

HRID 1295675Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1295675
C(OC(N1CCN([C:14](=[O:26])[NH:15][CH:16]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)[CH2:17][OH:18])CC1)=O)(C)(C)C.F[C:28](F)(F)[C:29](O)=O.[Cl:34][C:35]1[N:40]=[C:39](Cl)[C:38]([Cl:42])=[CH:37][N:36]=1>C(Cl)Cl>[Cl:25][C:21]1[CH:20]=[C:19]([CH:16]([NH:15][C:14]([CH:29]2[CH2:28][CH2:14][N:15]([C:39]3[C:38]([Cl:42])=[CH:37][N:36]=[C:35]([Cl:34])[N:40]=3)[CH2:16][CH2:17]2)=[O:26])[CH2:17][OH:18])[CH:24]=[CH:23][CH:22]=1

Komponenten

5

Edukt 3

HCID 6422Trifluoroacetic acidHCID 2372592,4,5-TrichloropyrimidineHCID 694145564-[1-(3-Chloro-phenyl)-2-hydroxy-ethylcarbamoyl]-piperazine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 866013611-(2,5-Dichloro-pyrimidin-4-yl)-piperidine-4-carboxylic acid [1-(3-chloro-phenyl)-2-hydroxy-ethyl]-amide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

4-[1 -(3-Chloro-phenyl)-2-hydroxy-ethylcarbamoyl]-piperazine- 1-carboxylic acid tert-butyl ester was deprotected with 10% trifluoroacetic acid in methylene chloride by stirring overnight at ambient temperature. The reaction was concentrated in vacuo and the resulting TFA salt was dissolved in DMF (1 mL) and DIEA (0.25 mL). This mixture was heated with 2,4,5-trichloropyrimidine (52 mg. 0.28 mmol) at 80° C. for 18 hours. Purification by prep HPLC (Gilson: Column=CombiHT SB-C189 5 μM 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient) afforded the title compound as a yellow oil (47 mg) Rt=5.97 minutes; MS FIA 429.9 (M+1).

Aufarbeitung

  1. concentrationThe reaction was concentrated in vacuo
  2. dissolutionthe resulting TFA salt was dissolved in DMF (1 mL)
  3. customPurification by prep HPLC (Gilson: Column=CombiHT SB-C189 5 μM 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient)

Quellen und Nachweise

ORD-Eintrag
ord-0cd86aae0bcc488387d5491d8850ab71
Quelldatensatz
uspto-grants-2007_07
Patentnummer
US07244735B2

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