Sodium Carbonate → 1-(4'-Fluoro-biphenyl-4-ylmethyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

HRID 410333Notes

Reaction equation

HRID 410333 reaction equation
Br[C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]([CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[C:8]2=[NH:27])=[CH:4][CH:3]=1.[F:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CO.O1CCOCC1>[F:30][C:31]1[CH:36]=[CH:35][C:34]([C:2]2[CH:3]=[CH:4][C:5]([CH2:6][N:7]3[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=4[N:9]([CH2:16][CH2:17][CH2:18][O:19][C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[C:8]3=[NH:27])=[CH:28][CH:29]=2)=[CH:33][CH:32]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 462409921-(4-Bromo-benzyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

Product 1

HCID 585649931-(4'-Fluoro-biphenyl-4-ylmethyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamineYield 36%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21966525Dioxane MethanolSolvent

Conditions

Temperature
100 °C

Procedure

Nitrogen was bubbled through a mixture of 1-(4-bromo-benzyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (80 mg, 0.18 mmol) and 4-fluorophenyl boronic acid (37 mg, 0.26 mmol) in 3:1 MeOH/1,4-dioxane (3 ml) at rt for 10 min before a solution of 2M Na2CO3 (0.17 ml, 0.35 mmol) was introduced. The suspension was degassed for a further 2 min and then PdCl2(dppf) (14 mg, 0.02 mmol) was added. The reaction mixture was sealed and heated to 100° C. where it was maintained for 16 h. After this time, the suspension was cooled to rt and filtered through Celite®. The filtrate was concentrated under reduced pressure and the crude product that remained was purified by preparative HPLC to provide 1-(4′-fluoro-biphenyl-4-ylmethyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (30 mg, 36%). HPLC-MS 470 [M+1]+.

Workup

  1. additionwas introduced
  2. customThe suspension was degassed for a further 2 min
  3. customThe reaction mixture was sealed
  4. temperaturewas maintained for 16 h
  5. temperatureAfter this time, the suspension was cooled to rt
  6. filtrationfiltered through Celite®
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe crude product that remained was purified by preparative HPLC

Sources & evidence

ORD record
ord-a3b2d438db784077afe5755b7ad0b0d6
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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