Sodium Carbonate → HCID 57531208, compound

HRID 1454919Notes

Reaction equation

HRID 1454919 reaction equation
Br[CH:2]=[C:3]1[C:16]2[CH:15]=[CH:14][C:13]([F:17])=[CH:12][C:11]=2[S:10][C:9]2[C:4]1=[CH:5][CH:6]=[C:7]([F:18])[CH:8]=2.CC1(C)C(C)(C)OB([C:27]2[CH:36]=[CH:35][C:30]3[NH:31][C:32](=[O:34])[NH:33][C:29]=3[CH:28]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[F:18][C:7]1[CH:6]=[CH:5][C:4]2[C:3](=[CH:2][C:27]3[CH:36]=[CH:35][C:30]4[NH:31][C:32](=[O:34])[NH:33][C:29]=4[CH:28]=3)[C:16]3[C:11]([S:10][C:9]=2[CH:8]=1)=[CH:12][C:13]([F:17])=[CH:14][CH:15]=3

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 438110655-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2(3H)-oneHCID 57531215HCID 57531215, compound

Product 1

HCID 57531208HCID 57531208, compoundYield 17.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

Mix 9-bromomethylene-3,6-difluoro-9H-thioxanthene (104 mg, 0.32 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)- 1,3-dihydro-benzoimidazol-2-one (76 mg, 0.29 mmol), and Na2CO3 (2M/water, 363 μL, 0.73 mmol) in dioxane (2 mL) and sparge with nitrogen for 5 min. Add Pd(PPh3)4 (17 mg, 0.015 mmol), seal vial, and heat to 95° C. overnight. Concentrate and dilute with water (3 mL) and ethyl acetate (10 mL). Load mixture onto a Varian ChemElut CE1005 solid-phase extraction cartridge. Elute, collect, and concentrate 50 mL ethyl acetate. Purify on silica gel (50-60% THF/hexanes), then re-purify by semi-prep reverse-phase HPLC (10-95% CH3CN/H2O, 0.1% TFA added) to afford 19 mg (17%) of the title compound as a yellow foam. MS [ES] 379 (M+H), 377 (M−H); HPLC shows 100% purity;, 1H-NMR (DMSO-d6) δ 10.67 (s, 1H), 10.54 (s, 1H), 7.89 (dd, 1H, J=8.6, 5.5 Hz), 7.53 (dd, 1H, J=9.0, 2.9 Hz), 7.47 (dd, 1H, J=8.8, 2.6 Hz), 7.27 (m, 2H), 7.02 (m, 2H), 6.86 (dd, 2H, J=11.5, 8.4 Hz), 6.78 (s, 1H).

Workup

  1. customsparge with nitrogen for 5 min
  2. concentrationConcentrate
  3. additiondilute with water (3 mL) and ethyl acetate (10 mL)
  4. extractionLoad mixture onto a Varian ChemElut CE1005 solid-phase extraction cartridge
  5. washElute
  6. customcollect
  7. concentrationconcentrate 50 mL ethyl acetate
  8. customPurify on silica gel (50-60% THF/hexanes)
  9. customre-purify by semi-prep reverse-phase HPLC (10-95% CH3CN/H2O, 0.1% TFA added)

Sources & evidence

ORD record
ord-2a1f17fbb1c64db48ed3b7a7f5b5158a
Source dataset
uspto-grants-2009_01
Patent number
US07482344B2

Reaction notes

Loading…