Lithium Chloride → 6-(4-(benzyloxy)-3-fluorophenyl)-1-phenyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one

HRID 1676391Notes

Reaction equation

HRID 1676391 reaction equation
Br[C:2]1[C:7](=[O:8])[N:6]2[CH2:9][CH2:10][N:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:5]2=[N:4][CH:3]=1.[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][C:27]=1[F:35])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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>[CH2:18]([O:25][C:26]1[CH:31]=[CH:30][C:29]([C:2]2[C:7](=[O:8])[N:6]3[CH2:9][CH2:10][N:11]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:5]3=[N:4][CH:3]=2)=[CH:28][C:27]=1[F:35])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 27377884-Benzyloxy-3-fluorophenylboronic AcidHCID 673474496-bromo-1-phenyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one

Product 1

HCID 673466776-(4-(benzyloxy)-3-fluorophenyl)-1-phenyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 6-bromo-1-phenyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one (0.075 g, 0.257 mmol), 4-(benzyloxy)-3-fluorophenylboronic acid (0.076 g, 0.308 mmol), Pd(PPh3)4 (0.015 g, 0.013 mmol) and lithium chloride (0.044 g, 1.03 mmol) in dioxane (2 mL) and 2M aqueous Na2CO3 was stirred at 100° C. for 30 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 10:1 CH2Cl2/EtOAc. The product was obtained (84 mg; 79%) as a pale tan solid. 1H-NMR (400 MHz, DMSO-d6) δ 8.04 (s, 1H), 7.82 (m, 2H), 7.61 (dd, 1H), 7.50-7.31 (m, 8H), 7.25 (t, 1H), 7.14 (t, 1H), 5.21 (s, 2H), 4.20 (m, 4H). LRMS (APCI pos) m/e 414 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe layers were separated
  4. extractionthe aqueous layer was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography
  9. washeluting with 10:1 CH2Cl2/EtOAc
  10. customThe product was obtained (84 mg; 79%) as a pale tan solid

Sources & evidence

ORD record
ord-8667f3ff77f5439fb1b3b65df307e34e
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

Loading…