Potassium Phosphate, Tribasic → 3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60166

Reaktionsgleichung

Reaktionsgleichung von HRID 60166
[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:29])[CH2:25][CH:26]([CH3:28])[CH3:27])=[C:20](Cl)[N:21]=[CH:22][C:15]=2[N:14]([CH3:30])[C:13]1=[O:31])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH:32]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O)([CH3:34])[CH3:33].[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:29])[CH2:25][CH:26]([CH3:28])[CH3:27])=[C:20]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[CH:32]([CH3:34])[CH3:33])[N:21]=[CH:22][C:15]=2[N:14]([CH3:30])[C:13]1=[O:31])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 27734772-Isopropylbenzeneboronic acidHCID 1317370773-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione2×

Produkt 1

HCID 1317370833-(3-(tert-butyldimethylsilyloxy)propyl)-5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dioneAusbeute 14,3 %

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-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (See Compound 48, step 1, 130 mg, 0.277 mmol), 2-isopropylphenyl boronic acid (90.8 mg, 0.554 mmol), aq. 2M K3PO4 (0.68 ml, 1.35 mmol) in dioxane (1 mL) and water (0.2 mL) was added Pd(dppf)Cl2 (8 mg, 0.01 mmol). The reaction was degassed with nitrogen (3×), heated at 120° C. (MW) for 1.5 h, cooled to RT, diluted with EA (10 mL) and water (2 mL) and filtered. The filtrate was concentrated to a residue which was purified by Prep TLC PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(1-hydroxy-3-methylbutyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (22 mg, 14.3% yield) as a colorless oil. LCMS: MH+ 554 and TR=2.415 min.

Aufarbeitung

  1. customThe reaction was degassed with nitrogen (3×)
  2. temperatureheated at 120° C. (MW) for 1.5 h
  3. additiondiluted with EA (10 mL) and water (2 mL)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated to a residue which
  6. customwas purified by Prep TLC PE/EA (2:1)

Quellen und Nachweise

ORD-Eintrag
ord-4ebb7317717d4a3da8784b95529c9ffa
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440973B2

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