Cesium carbonate → 6-(2-methoxy-pyrimidin-4-yl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one

HRID 538242Notes

Reaction equation

HRID 538242 reaction equation
[O:1]([CH2:8][C:9]1[N:10]=[C:11]2[CH:16]=[CH:15][NH:14][C:13](=[O:17])[N:12]2[CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([O:26][CH3:27])[N:21]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:27][O:26][C:22]1[N:23]=[C:24]([N:14]2[CH:15]=[CH:16][C:11]3=[N:10][C:9]([CH2:8][O:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[CH:18][N:12]3[C:13]2=[O:17])[CH:25]=[CH:20][N:21]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5752304-Chloro-2-methoxypyrimidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 1360357622-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one

Product 1

HCID 682909496-(2-methoxy-pyrimidin-4-yl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-oneYield 20%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

Palladium(II)acetate (4.2 mg, 0.019 mmol) was added to a stirred suspension of 2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one (150 mg, 0.62 mmol), 4-chloro-2-methoxy-pyrimidine (107.9 mg, 0.75 mmol), Cs2CO3 (283.6 mg, 0.87 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triiso-propyl-1,1′-biphenyl (26.7 mg, 0.056 mmol) in 1,4-dioxane (2 mL) under nitrogen and in a sealed tube. The mixture was stirred at 100° C. for 3 days and at 140° C. for 15 minutes under microwave irradiation. The solvent was evaporated in vacuo and the crude product was purified by flash column chromatography (silica; AcOEt in DCM with a gradient of 0/100 to 100/0). The desired fractions were collected and the solvents evaporated in vacuo. The product was triturated with diethyl ether to yield 6-(2-methoxy-pyrimidin-4-yl)-2-phenoxymethyl-6H-imidazo[1,2-c]pyrimidin-5-one (43 mg, 20% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 4.09 (s, 3H), 5.18 (d, J=0.9 Hz, 2H), 6.77 (dd, J=8.2, 0.6 Hz, 1H), 6.95-7.06 (m, 3H), 7.27-7.36 (m, 2H), 7.85 (d, J=0.7 Hz, 1H), 7.91 (d, J=5.5 Hz, 1H), 8.24 (d, J=8.1 Hz, 1H), 8.65 (d, J=5.5 Hz, 1H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe crude product was purified by flash column chromatography (silica
  3. customThe desired fractions were collected
  4. customthe solvents evaporated in vacuo
  5. customThe product was triturated with diethyl ether

Sources & evidence

ORD record
ord-421184aefb754bf094ad74f8ceb3433a
Source dataset
uspto-grants-2014_10
Patent number
US08865725B2

Reaction notes

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