Diisopropylethylamine → (1,1-dimethylethyl) 3-[(6-chloro-5-ethyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy)carbonyl]alaninate

HRID 2358199Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2358199
C(N(C(C)C)CC)(C)C.Cl[C:11]1[C:16]([CH2:17][CH3:18])=[C:15]([Cl:19])[N:14]=[CH:13][N:12]=1.[CH3:20][C:21]([O:24][C:25](=[O:40])[C@H:26]([CH2:38][NH2:39])[NH:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])([CH3:23])[CH3:22].C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[Cl:19][C:15]1[N:14]=[CH:13][N:12]=[C:11]([NH:39][CH2:38][C@@H:26]([C:25]([O:24][C:21]([CH3:23])([CH3:22])[CH3:20])=[O:40])[NH:27][C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[C:16]=1[CH2:17][CH3:18]

Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10803731(S)-tert-Butyl 3-amino-2-(((benzyloxy)carbonyl)amino)propanoateHCID 218284324,6-Dichloro-5-ethylpyrimidine

Produkt 1

HCID 12094339(1,1-dimethylethyl) 3-[(6-chloro-5-ethyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy)carbonyl]alaninateAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

10 ml of diisopropylethylamine is added to a mixture of 3.8 g (21 mmoles) of 4,6-dichloro-5-ethyl-pyrimidine and 4.4 g (15 mmoles) of (1,1-dimethylethyl)-3-amino-N-[(phenylmethoxy)carbonyl]alaninate (prepared according to J. Med. Chem. (2001), 44(8), 1158-1176) in 50 ml of dimethylformamide, then this mixture is heated at 120° C. for 6 hours. Then the dimethylformamide is eliminated under vacuum and the residue is taken up in a mixture of ethyl acetate, water and a saturated solution of sodium bicarbonate. The organic phase is decanted then dried over magnesium sulphate and the solvent is eliminated by evaporation under vacuum. The residue is chromatographed on silicagel eluting with a gradient of 100% heptane to heptane-ethyl acetate 50-50. 4.7 g (Yield=70%) of expected product is obtained in the form of an oil.

Aufarbeitung

  1. customThe organic phase is decanted
  2. dry with materialthen dried over magnesium sulphate
  3. customthe solvent is eliminated by evaporation under vacuum
  4. customThe residue is chromatographed
  5. washon silicagel eluting with a gradient of 100% heptane to heptane-ethyl acetate 50-50

Quellen und Nachweise

ORD-Eintrag
ord-7a1b45dcea9d416ba88a0578e05ffdad
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07763621B2

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