Sodium Carbonate → (S)-tert-butyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate

HRID 1626544Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1626544
Cl[C:2]1[N:3]=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][C@@H:20]2[CH3:25])[C:5]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:6]=2[N:7]=1.[CH2:26]([NH:28][C:29](=[O:46])[NH:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=1)[CH3:27].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.O>[CH2:26]([NH:28][C:29](=[O:46])[NH:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[N:3]=[C:4]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][C@@H:20]3[CH3:25])[C:5]3[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][C:6]=3[N:7]=2)=[CH:33][CH:32]=1)[CH3:27]

Komponenten

5

Edukt 3

HCID 10340Sodium CarbonateHCID 44119377N-Ethyl-N'-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 59239275Pyrido[3,4-d]pyriMidine-7(6H)-carboxylic acid, 2-chloro-5,8-dihydro-4-[(3S)-3-Methyl-4-Morpholinyl]-, 1,1-diMethylethyl ester2×

Produkt 1

HCID 59239149(S)-tert-butyl 2-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylateAusbeute 59,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 86587095Dimethoxyethane ethanol waterLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of (S)-tert-butyl 2-chloro-4-(3-methylmorpholino)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate (intermediate 4) (576 mg, 1.56 mmol) and 4-(3-ethylureido)phenylboronic acid pinacol ester (498 mg, 1.72 mmol) in DME/EtOH/H2O (12/5/3) (15 mL) was added Pd(PPh3)2(Cl)2 (55 mg, 0.078 mmol) and Na2CO3 (496 mg, 4.68 mmol). The reaction mixture was then heated by microwave at 120° C. for 1 h. The crude reaction mixture was then partitioned between water and EtOAc, the phases separated and the organic layer washed with aqueous NaHCO3 and brine, dried over magnesium sulfate, filtered and the solvent removed in vacuo. The residue was purified by flash chromatography (20-50% EtOAc/Petroleum Ether 40-60) to yield a yellow solid (460 mg, 59%).

Aufarbeitung

  1. customThe crude reaction mixture
  2. customwas then partitioned between water and EtOAc
  3. customthe phases separated
  4. washthe organic layer washed with aqueous NaHCO3 and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by flash chromatography (20-50% EtOAc/Petroleum Ether 40-60)

Quellen und Nachweise

ORD-Eintrag
ord-76deec4061e542ffb62dc757fa2245bd
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785457B2

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