Sodium Carbonate → 5-(4-chlorobenzyl)-6-(3-fluorophenyl)-3-(3-hydroxy propyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60460

Reaktionsgleichung

Reaktionsgleichung von HRID 60460
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[C:15](Br)[CH:16]=[N:17][C:10]=2[N:9]([CH3:27])[C:8]1=[O:28])=O.[F:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CCO.CC(=O)OCC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][C:14]2[C:11]3[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:28])[N:9]([CH3:27])[C:10]=3[N:17]=[CH:16][C:15]=2[C:34]2[CH:33]=[CH:32][CH:31]=[C:30]([F:29])[CH:35]=2)=[CH:21][CH:22]=1

Komponenten

9

Edukt 3

HCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 1188758893-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Produkt 1

HCID 1188755565-(4-chlorobenzyl)-6-(3-fluorophenyl)-3-(3-hydroxy propyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 3-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (70 mg, 0.15 mmol), 3-fluorophenylboronic acid (31 mg, 0.22 mmol), Na2CO3(0.6 ml) in THF (3.2 mL) and EtOH (1.6 mL) was added Pd(PPh3)4 (25 mg, 0.015 mmol). The reaction was heated at 100° C. for 18 h, cooled to RT then diluted with EA (20 mL) and water (20 mL). The organic layer was dried over Na2SO4, and concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-6-(3-fluorophenyl)-3-(3-hydroxy propyl)-1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (50 mg, 85% yield) as white solid. 1H NMR (CDCl3) δ: 8.53 (s, 1H), 7.36 (dd, J=8.0, 6.0 Hz, 1H), 7.19-7.06 (m, 3H), 6.97-6.86 (m, 2H), 6.77 (d, J=8.3 Hz, 2H), 4.63 (s, 2H), 4.19 (t, J=6.1 Hz, 2H), 3.78 (s, 3H), 3.47 (dd, J=11.7, 6.1 Hz, 2H), 2.92 (t, J=6.9 Hz, 1H), 1.96-1.77 (m, 2H). LCMS: MH+ 454 and TR=3.00 min.

Aufarbeitung

  1. temperaturecooled to RT
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated to a residue which
  4. customwas purified by Prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-93bec82dd4d04d06a7a781f48d68aa3b
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440972B2

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