2,4-Dichloro-5-(trifluoromethyl)pyrimidine → (R)-tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

HRID 2093026

Reaktionsgleichung

Reaktionsgleichung von HRID 2093026
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])=[CH:4][CH:3]=1.Cl[C:19]1[N:24]=[C:23]([Cl:25])[C:22]([C:26]([F:29])([F:28])[F:27])=[CH:21][N:20]=1>ClCCCl.CC(O)(C)C.[Zn+2].[Br-].[Br-]>[Cl:25][C:23]1[C:22]([C:26]([F:28])([F:27])[F:29])=[CH:21][N:20]=[C:19]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])=[CH:4][CH:3]=2)[N:24]=1

Komponenten

5

Edukt 2

HCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 10633571(R)-[1-(4-Amino-phenyl)-ethyl]-carbamic acid tert-butyl ester

Produkt 1

HCID 57584789(R)-tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 10421208Zinc bromideKatalysatorHCID 21868497Tert-butyl alcohol 1,2-dichloroethaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

C2 (690 mg, 2.92 mmol) was dissolved in 10 mL DCE:t-BuOH (1:1 vol:vol), and the resultant solution was treated with ZnBr2 (1.97 g, 8.76 mmol) and 2,4-dichloro-5-(trifluoromethyl)pyrimidine (748 mg, 3.45 mmol). The resultant mixture was then treated drop-wise with TEA (406 ml, 2.92 mmol), and the mixture was allowed to stir at 25° C. for about 20 hours. The reaction mixture was concentrated, and the resultant residue was treated with EtOAc. The resultant solution was washed with water and brine, and dried over MgSO4. The mixture was then filtered, concentrated, and purified by column chromatography eluting with 22% EtOAc/Heptane. The product-containing eluents were combined and concentrated to provide C3 as a white solid. Yield: 680 mg, 56%. MS-415.2. 1H NMR (500 MHz, DMSO) δ: 10.59 (s, 1H), 8.74 (s, 1H), 7.53 (d, 2H), 7.31 (d, 1H), 7.23 (d, 2H), 4.54 (m, 1H), 1.33 (s, 9H), 1.25 (d, 3H).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. additionthe resultant residue was treated with EtOAc
  3. washThe resultant solution was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationThe mixture was then filtered
  6. concentrationconcentrated
  7. custompurified by column chromatography
  8. washeluting with 22% EtOAc/Heptane
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-9fe62c7d26124addbaebfbdaf0419c51
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08440822B2

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