Cyanogen Bromide → HCID 178508161, compound

HRID 2367111Notes

Reaction equation

HRID 2367111 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:26])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[N:10]2[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:5]=[CH:6][C:7]=1[NH2:8].[N:27]#[C:28]Br>C(O)C>[NH2:27][C:28]1[NH:8][C:7]2[CH:6]=[CH:5][C:4]([C:9]3([OH:26])[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[C:11](=[O:18])[N:10]3[CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:3][C:2]=2[N:1]=1

Participants

4

Reactant 2

HCID 10476Cyanogen BromideHCID 67044654HCID 67044654, compound

Product 1

HCID 178508161HCID 178508161, compoundYield 1.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 3-(3,4-diaminophenyl)-3-hydroxy-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one (613 mg, 1.77 mmol) and cyanogen bromide (188 mg, 1.77 mmol) in anhydrous ethanol (10 mL) was heated to 60° C. for 16 h. The reaction mixture was cooled and partitioned between ethyl acetate (200 mL) and saturated aqueous sodium bicarbonate. The organic layer was washed with water and brine then dried over anhydrous magnesium sulfate, filtered and the filtrate concentrated in vacuo. The residue was purified by reverse phase HPLC. To the combined fractions were added 6N aqueous hydrochloric acid (10 mL) and heated for 10 mins, at which time saturated aqueous sodium bicarbonate was added until pH reached 7. To the aqueous layer was added ethyl acetate (300 mL) and then separated. The organic layer was washed with brine and dried over magnesium sulfate, filtered and the filtrate concentrated in vacuo to afford 3-(2-amino-1H-benzimidazol-5-yl)-3-hydroxy-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one (10.3 mg). 1H NMR (400 MHz, d6-DMSO): 7.76 (d, 1H), 7.59-7.52 (m, 2H), 7.26-7.18 (m, 3H), 7.12-7.09 (m, 5H), 7.03-7.01 (m, 1H), 4.43 (d, 1H), 4.21 (d, 1H), 3.48-3.39 (m, 1H); MS (EI) for C22H18N4O2: 371 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between ethyl acetate (200 mL) and saturated aqueous sodium bicarbonate
  3. washThe organic layer was washed with water and brine
  4. dry with materialthen dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo
  7. customThe residue was purified by reverse phase HPLC
  8. additionTo the combined fractions were added 6N aqueous hydrochloric acid (10 mL)
  9. temperatureheated for 10 mins, at which time saturated aqueous sodium bicarbonate
  10. additionwas added until pH
  11. additionTo the aqueous layer was added ethyl acetate (300 mL)
  12. customseparated
  13. washThe organic layer was washed with brine
  14. dry with materialdried over magnesium sulfate
  15. filtrationfiltered
  16. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-23812c47fded4030addce80d2fe4684d
Source dataset
uspto-grants-2014_04
Patent number
US08697737B2

Reaction notes

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