Dicyclohexylcarbodiimide → 3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoic acid 2-morpholin-4-yl-ethyl ester

HRID 2110749Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2110749
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][NH:11][C:12]1[N:17]=[C:16]([O:18][CH3:19])[N:15]=[C:14]([C:20]2[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=2)[C:23]([OH:25])=[O:24])[CH:13]=1.O[CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.C1COCC1.C(Cl)Cl>[N:32]1([CH2:31][CH2:30][O:24][C:23](=[O:25])[C:22]2[CH:26]=[CH:27][CH:28]=[C:20]([C:14]3[CH:13]=[C:12]([NH:11][CH2:10][CH2:9][C:3]4[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=4[Cl:1])[N:17]=[C:16]([O:18][CH3:19])[N:15]=3)[CH:21]=2)[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1

Komponenten

6

Edukt 3

HCID 10868DicyclohexylcarbodiimideHCID 611632-MorpholinoethanolHCID 533205273-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoic acid

Produkt 1

HCID 115266143-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoic acid 2-morpholin-4-yl-ethyl esterAusbeute 43,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 21919333Tetrahydrofurane dichloromethaneLösungsmittel

Versuchsvorschrift

4-Dimethylaminopyridine (4.4 mg, 0.036 mmol) is added to a stirred solution of 3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoic acid (100 mg, 0.24 mmol), N-(2-hydroxyethyl) morpholine (29.07 μL, 0.24 mmol) and 1,3-dicyclohexylcarbodiimide (0.31 mL, 1 M solution in DCM) in dry THF/DCM (6 mL, 1:1) and the reaction mixture is stirred for 5.5 hours at room temperature under nitrogen atmosphere. The mixture is filtered over a pad of Celite and the filtrate concentrated under reduced pressure. The residue is dissolved EtOAc (30 mL), washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue is purified by chromatography (SiO2 packed column) eluting with ethyl acetate/heptane to afford 3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzoic acid 2-morpholin-4-yl-ethyl ester (56 mg, Example 75). LCMS: RT=2.07 minutes, MS: 534 (M+H); 1H NMR, (300 MHz, CDCl3): □8.62 (1H, s), 8.3 (1H, d, J=3.5 Hz), 8.1 (1H, d, J=3.5 Hz), 7.55 (1H, t, J=3.5 Hz), 7.42 (1H, s), 7.2 (2H, s), 6.48 (1H, s), 5.04 (1H, b), 4.5 (2H, t, J=2 Hz), 4.05 (3H, s), 3.72 (6H, t, J=2 Hz), 3.1 (2H, t, J=2 Hz), 2.8 (2H, t, 2 Hz), 2.6 (4H, t, 2 Hz).

Aufarbeitung

  1. filtrationThe mixture is filtered over a pad of Celite
  2. concentrationthe filtrate concentrated under reduced pressure
  3. dissolutionThe residue is dissolved EtOAc (30 mL)
  4. washwashed with saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue is purified by chromatography (SiO2 packed column)
  9. washeluting with ethyl acetate/heptane

Quellen und Nachweise

ORD-Eintrag
ord-8ec65d71d71a4033aedcfd77e0e9f249
Quelldatensatz
uspto-grants-2009_04
Patentnummer
US07517889B2

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