Sodium Carbonate → 5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60485

Reaktionsgleichung

Reaktionsgleichung von HRID 60485
Br[C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1[CH:25]([C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][N:28]=1)[OH:26].[F:34][C:35]([F:47])([F:46])[O:36][C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][CH:42]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([CH:25]([OH:26])[C:3]2[C:4]3[C:9](=[O:10])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][O:16]4)[C:7](=[O:21])[N:6]([CH3:22])[C:5]=3[N:23]=[CH:24][C:2]=2[C:39]2[CH:40]=[CH:41][CH:42]=[C:37]([O:36][C:35]([F:34])([F:46])[F:47])[CH:38]=2)=[N:28][CH:29]=1

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 1188755266-bromo-5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Produkt 1

HCID 1188755555-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneAusbeute 35,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 6-bromo-5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (75 mg, 0.138 mmol) in toluene (4 mL) and EtOH 1.3 mL) was added 3-(trifluoromethoxy)phenylboronic acid (43 mg, 0.208 mmol), Pd(dppf)Cl2 (10.7 mg) and aq. Na2CO3 (1M, 0.57 mL). The reaction was heated at 100° C. for 18 h, cooled to RT and filtered. The filtrate was concentrated and dried to a residue which was purified by Prep TLC eluted with PE/EA (4:1) to give 5-((5-chloropyridin-2-yl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 35.2% yield) as a solid. LCMS: MH+ 621 and TR=2.047 min.

Aufarbeitung

  1. temperaturecooled to RT
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customdried to a residue which
  5. customwas purified by Prep TLC
  6. washeluted with PE/EA (4:1)

Quellen und Nachweise

ORD-Eintrag
ord-9202c7065b8b4ec9a3617819e1ac2623
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440972B2

Verknüpfte Notizen

Wird geladen…