Potassium Phosphate, Tribasic → 3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(hydroxy(phenyl)methyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl)pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60176

Reaktionsgleichung

Reaktionsgleichung von HRID 60176
[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([CH:24]([OH:31])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:20](Cl)[N:21]=[CH:22][C:15]=2[N:14]([CH3:32])[C:13]1=[O:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[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.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([CH:24]([OH:31])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:20]([C:39]3[CH:40]=[CH:41][CH:42]=[C:37]([O:36][C:35]([F:34])([F:46])[F:47])[CH:38]=3)[N:21]=[CH:22][C:15]=2[N:14]([CH3:32])[C:13]1=[O:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 1317370873-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(hydroxy(phenyl)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H, 3H)-dione

Produkt 1

HCID 1317370883-(3-(tert-butyldimethylsilyloxy)propyl)-5-(hydroxy(phenyl)methyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl)pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dioneAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(hydroxy(phenyl)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (400 mg, 0.817 mmol), 3-(trifluoromethoxy)phenylboronic acid (336.9 mg, 1.635 mmol), aq. 2M K3PO4 (2 ml, 4.085 mmol) in dioxane (10 mL) and water (2 mL) was added Pd(dppf)Cl2 (21 mg, 0.0288 mmol). The reaction was degassed with nitrogen (3×), heated at 120° C. (MW) for 2 h, cooled to RT, diluted with EA (20 mL) and water (8 mL) and filtered through Celite. The filtrate was concentrated to a residue which was purified by Prep TLC eluted with PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(hydroxyl(phenyl)methyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl)pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (220 mg, 44% yield) as colorless oil. LCMS: MH+ 616 and TR=2.334 min.

Aufarbeitung

  1. customThe reaction was degassed with nitrogen (3×)
  2. temperatureheated at 120° C. (MW) for 2 h
  3. additiondiluted with EA (20 mL) and water (8 mL)
  4. filtrationfiltered through Celite
  5. concentrationThe filtrate was concentrated to a residue which
  6. customwas purified by Prep TLC
  7. washeluted with PE/EA (2:1)

Quellen und Nachweise

ORD-Eintrag
ord-7be2c8ed69274e659bd5f1856f91b0c0
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440973B2

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