Cesium carbonate → 2-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester

HRID 216180

Reaktionsgleichung

Reaktionsgleichung von HRID 216180
[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]([C:26]([CH3:31])([CH3:30])[C:27]([OH:29])=[O:28])[CH:23]=[CH:24][CH:25]=2)[CH:13]=1.[C:32](=[O:40])([O:37][CH2:38][CH3:39])[O:33][CH:34](Cl)[CH3:35].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C)C=O>[CH2:34]([O:33][C:32]([O:37][CH:38]([O:28][C:27](=[O:29])[C:26]([C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([C:14]2[CH:13]=[C:12]([NH:11][CH2:10][CH2:9][C:3]3[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=3[Cl:1])[N:17]=[C:16]([O:18][CH3:19])[N:15]=2)[CH:21]=1)([CH3:31])[CH3:30])[CH3:39])=[O:40])[CH3:35]

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 162095Carbonic acid, 1-chloroethyl ethyl esterHCID 11669780Pgd2-IN-1

Produkt 1

HCID 576360192-(3-{6-[2-(2,4-Dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a solution of 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [100 mg, 0.218 mmol, Example 49(b)] in dimethylformamide (2 mL) is added 1-chloroethyl ethyl carbonate (0.053 mL, 0.392 mmol) and Cs2CO3 (142 mg, 0.436 mmol). The mixture is heated under microwave at 110° C. for 10 minutes, quenched with water, and extracted with ethyl acetate. Combined organic layers are washed with brine, dried over sodium sulfate and concentrated. The residue is subjected to silica gel chromatography eluting with 0 to 40% EtOAc in heptane to obtain 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester as an oil which is treated with 1M hydrogen chloride in ether affording 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester hydrochloride [80 mg, 64%, Example 50] as a solid. LC/MS: RT=2.94 minutes, MS: 576 (M+H). 1H NMR [300 MHz, (CD3)2SO]: □7.36-7.8 (7H, m), 6.64 (1H, q), 6.6 (1H, s), 4.05 (2H, q), 3.96 (3H, s), 3.68 (2H, m), 3 (2H, m), 1.57 (6H, s), 1.38 (3H, d), 1.15 (3H, t). IC50=4 nM

Aufarbeitung

  1. customquenched with water
  2. extractionextracted with ethyl acetate
  3. washCombined organic layers are washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. washeluting with 0 to 40% EtOAc in heptane

Quellen und Nachweise

ORD-Eintrag
ord-765e24a6f3d048958ed52b94c1964f3f
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193183B2

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