Sodium Hydroxide → 3-(4-Bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamine

HRID 410357Notes

Reaction equation

HRID 410357 reaction equation
Br.[Br:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][N:8]2[C:12]3[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:11]=3[N:10]([CH2:18][CH2:19][CH2:20][O:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:9]2=[NH:29])=[CH:5][CH:4]=1.[OH-].[Na+]>CCOC(C)=O>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:11]=3[N:10]([CH2:18][CH2:19][CH2:20][O:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:9]2=[NH:29])=[CH:30][CH:31]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 1317316393-(4-Bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamine, hydrobromide salt

Product 1

HCID 585649693-(4-Bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamineYield 100%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

3-(4-Bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamine, hydrobromide salt (20 mg, 0.036 mmol) was partitioned between aqueous NaOH and EtOAc. The organic phase was separated, dried (Na2SO4) and concentrated under reduced pressure to provide 3-(4-bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamine (0.036 mmol). To a degassed solution of Pd(OAc)2 (0.04 mg, 0.16 □mol) and BINAP (0.44 mg, 0.71 mmol) in toluene (8 ml) at 40° C. was added 1-biphenyl-2-ylmethyl-piperazine (18 mg, 0.071 mmol) followed by 3-(4-bromo-benzyl)-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydrobenzoimidazol-2-ylideneamine (0.036 mmol) and sodium t-butoxide (4.8 mg, 0.05 mmol). The suspension was then heated to 130° C. where it was maintained for 20 h. After this time, the mixture was filtered and then the filtrate was partitioned between H2O and EtOAc. The organic phase was separated and concentrated under reduced pressure to provide the crude product. Purification by preparative HPLC gave 3-[4-(4-biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-1-[3-(4-fluoro-phenoxy)-propyl]-5-methyl-1,3-dihydro-benzoimidazol-2-ylideneamine (2.5 mg, 11%). HPLC-MS 640 [M+1]+, 320 (100%).

Workup

  1. customThe organic phase was separated
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-74378b2f1cdc44cfaea4047f7ba217d3
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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