Potassium Phosphate, Tribasic → 3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-6-(2-phenylcyclopropyl)pyrimidin-4(3H)-one

HRID 2059869Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2059869
C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.Cl[C:21]1[N:26]=[CH:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]([OH:38])([CH3:37])[CH3:36])=[C:29]([O:39][CH3:40])[CH:28]=2)[C:23](=[O:41])[CH:22]=1.[C:42]1([CH:48]2[CH2:50][CH:49]2B(O)O)[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[OH:38][C:35]([CH3:37])([CH3:36])[CH2:34][O:33][C:30]1[CH:31]=[CH:32][C:27]([N:24]2[C:23](=[O:41])[CH:22]=[C:21]([CH:49]3[CH2:50][CH:48]3[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[N:26]=[CH:25]2)=[CH:28][C:29]=1[O:39][CH3:40]

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 12982400(2-Phenylcyclopropyl)boronic acidHCID 585799166-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one

Produkt 1

HCID 585798413-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-6-(2-phenylcyclopropyl)pyrimidin-4(3H)-oneAusbeute 23,49 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Tricyclohexyl phosphine (10 μL, 9.24 μmol) was added under nitrogen to a mixture of 6-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one Part A of Procedure 11 (10 mg, 0.031 mmol), 2-phenylcyclopropylboronic acid (5.5 mg, 0.034 mmol), palladium (II) acetate (2 mg, 6.16 μmol), and potassium phosphate, tribasic (20 mg, 0.09 mmol) in toluene (0.16 mL), and water (0.07 mL). The reaction stirred at 100° C. for 2 hours. The reaction mixture was filtered and concentrated to afford the crude product. The crude was purified using HPLC (C18 column/10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA) to afford the desired product 3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-6-(2-phenylcyclopropyl)pyrimidin-4(3H)-one K-1 (3 mg, 7.23 μmol, 23.49% yield) as a light yellow solid. LC/MS 407 (M+H)+, tR 0.92 min (method 5); 1H NMR (400 MHz, CHLOROFORM-d) δ 8.11 (1H, s), 7.28-7.41 (2H, m), 7.20-7.26 (1H, m), 7.13-7.19 (2H, m), 7.00 (1H, d), 6.85-6.90 (2H, m), 6.48 (1H, s), 3.88 (5H, br. s.), 2.60-2.66 (1H, m), 2.08-2.14 (1H, m), 1.75-1.81 (1H, m), 1.51-1.57 (1H, m), 1.37 (6H, s).

Aufarbeitung

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated
  3. customto afford the crude product
  4. customThe crude was purified

Quellen und Nachweise

ORD-Eintrag
ord-9caabd27b0534bec9ae6db7c91b9afa7
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08278316B2

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