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

HRID 2059877Notes

Reaction equation

HRID 2059877 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([O:20][CH3:21])[CH:9]=2)[C:4](=[O:22])[CH:3]=1.[CH2:23]([C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)[CH3:24].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:23]([C:25]1[CH:30]=[CH:29][C:28]([C:2]2[N:7]=[CH:6][N:5]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([O:20][CH3:21])[CH:9]=3)[C:4](=[O:22])[CH:3]=2)=[CH:27][CH:26]=1)[CH3:24]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734352Boronic acid, (4-ethylphenyl)-HCID 585799166-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one

Product 1

HCID 469274356-(4-ethylphenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-oneYield 69.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one Part A of Procedure 11 (11 mg, 0.03 mmol), 4-ethylphenylboronic acid (7.6 mg, 0.05 mmol), potassium phosphate tribasic (21.57 mg, 0.102 mmol), and PalladiumTetrakis (4 mg, 3.39 μmol) in DMF (0.5 mL) was stirred at 90° C. overnight. The reaction was diluted with CH2Cl2, filtered, and concentrated. The crude was purified using HPLC (Phen Luna Axia C18 5μ 10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA) to afford the desired product 6-(4-ethylphenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one M-1 (9.93 mg, 0.02 mmol, 69.1% yield) as a light yellow solid. LC/MS 395 (M+H)+, tR 0.95 min (method 5). 1H NMR (500 MHz, CHLOROFORM-d) d ppm 8.25 (1H, s), 7.93 (2H, d, J=8.32 Hz), 7.34 (2H, d, J=8.32 Hz), 7.02 (1H, d), 6.91-6.96 (3H, m), 3.90 (3H, s), 3.89 (2H, s), 2.74 (2H, q), 1.38 (6H, s), 1.30 (3H, t, J=7.63 Hz)

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. customThe crude was purified

Sources & evidence

ORD record
ord-1e182211781748d994a6dacee2bbf6cb
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Reaction notes

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