Sodium Carbonate → HCID 135589862, compound

HRID 422055Notes

Reaction equation

HRID 422055 reaction equation
Cl[C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[N:3]=1.[OH:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=[O:51].[Na+].[Na+]>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:21][C:22]1[CH:27]=[CH:26][C:25]([C:6]2[CH:5]=[C:4]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][CH2:16][CH2:17][CH:18]([CH3:20])[CH3:19])[NH:3][C:2](=[O:51])[N:7]=2)=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27343604-Hydroxyphenylboronic acidHCID 57445459HCID 57445459, compound

Product 1

HCID 135589862HCID 135589862, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2,4-dichloro-6-(2-(isopentyloxy)phenyl)pyrimidine (0.32 mmol, 100 mg) in 5 mL of THF was added 4-hydroxyphenylboronic acid (0.33 mmol, 46 mg), Pd(OAc)2 (4 mol %, 10 mg) and PPh3 (8 mol %, 9 mg) followed by Na2CO3 (1M, 1.20 mL). The reaction was heated to 60° C. for 2 hours, then concentrated in vacuo. 8 mL of conc. HCl was added to the reaction mixture which was heated to 90° C. Once the hydrolization was complete, the reaction was concentrated in vacuo. The residue was dissolved in methanol and passed through a stratosphere SPE cartridge (Polymer Labs) to remove Pd. Purification by HPLC (reverse-phase, acetonitrile/water with 0.01% ammonium acetate), followed by concentration in vacuo and lyophilization gave the title compound 4-(4-hydroxyphenyl)-6-(2-(isopentyloxy)phenyl)pyrimidin-2(1H)-one (35 mg, 30% yield). 1H NMR (400 MHz, d-4-MeOH): 8.03-7.97 (m, 2H), 7.67-7.63 (m, 1H), 7.56-7.51 (m, 1H), 7.22-7.18 (m, 2H), 7.15-7.10 (m, 1H), 6.93-6.90 (d, 2H), 4.17 (t, 2H), 1.85-1.70 (m, 3H), 0.95 (s, 3H), 0.93 (s, 3H). MS (EI) for C21H22N2O3: 351 (MH+).

Workup

  1. concentrationconcentrated in vacuo
  2. addition8 mL of conc. HCl was added to the reaction mixture which
  3. temperaturewas heated to 90° C
  4. concentrationthe reaction was concentrated in vacuo
  5. dissolutionThe residue was dissolved in methanol
  6. customto remove Pd
  7. customPurification by HPLC (reverse-phase, acetonitrile/water with 0.01% ammonium acetate)
  8. concentrationfollowed by concentration in vacuo and lyophilization

Sources & evidence

ORD record
ord-ef2d1073691249438b554118480e2eeb
Source dataset
uspto-grants-2012_01
Patent number
US08101625B2

Reaction notes

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