Potassium Phosphate, Tribasic → 5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60454

Reaktionsgleichung

Reaktionsgleichung von HRID 60454
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]([OH:30])[CH2:26][CH:27]([CH3:29])[CH3:28].[CH:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O)([CH3:33])[CH3:32].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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]>[OH:30][CH:25]([C:3]1[C:4]2[C:9](=[O:10])[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:7](=[O:21])[N:6]([CH3:22])[C:5]=2[N:23]=[CH:24][C:2]=1[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[CH:31]([CH3:33])[CH3:32])[CH2:26][CH:27]([CH3:28])[CH3:29]

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 27734772-Isopropylbenzeneboronic acidHCID 1188755166-bromo-5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Produkt 1

HCID 1188755495-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneAusbeute 42,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 6-bromo-5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (65 mg, 0.134 mmol) in dioxane (1 mL) was added (2-isopropylphenyl)boronic acid (88 mg, 0.536 mmol), Pd(dppf)Cl2 (10 mg) and aq. 2N K3PO4 (0.2 mL). The mixture was heated at 100° C. for 5 h, cooled to RT and filtered. The filtrate was concentrated and dried to a residue which was purified by chromatography eluted with PE/EA (10:1 to 6:1) to give 5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 42.7% yield) as a solid. LCMS: [M+-THP-OH] 423 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 chromatography
  6. washeluted with PE/EA (10:1 to 6:1)

Quellen und Nachweise

ORD-Eintrag
ord-6c9ea7b0b6de4f8ba4875b9f73bcab13
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440972B2

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