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

HRID 2059869Notes

Reaction equation

HRID 2059869 reaction equation
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]

Participants

8

Reactant 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

Product 1

HCID 585798413-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-6-(2-phenylcyclopropyl)pyrimidin-4(3H)-oneYield 23.49%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-9caabd27b0534bec9ae6db7c91b9afa7
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Reaction notes

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