Hydrochloric Acid → HCID 178482307, compound

HRID 2367086Notes

Reaction equation

HRID 2367086 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].[CH3:27][N:28]=[C:29]=S.Cl>O1CCCC1>[OH:26][C:9]1([C:4]2[CH:5]=[CH:6][C:7]3[NH:8][C:27]([NH:28][CH3:29])=[N:1][C:2]=3[CH:3]=2)[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:18])[N:10]1[CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 11167Methyl isothiocyanateHCID 67044654HCID 67044654, compound

Product 1

HCID 178482307HCID 178482307, compoundYield 3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 3-(3,4-diaminophenyl)-3-hydroxy-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one (100 mg, 0.289 mmol) and methyl isothiocyanate (31 mg, 0.434 mmol) in tetrahydrofuran (30 mL) was added 1-[3-dimethylamino)propyl]-3-ethylcarbodiimmide hydrochloride (89 mg, 0.462 mmol) at room temperature. The reaction mixture was heated to 65° C. and stirred for 3 h, at which time it was cooled to room temperature and partitioned with water and a mixture of acetonitrile-ethyl acetate (1:9, 200 mL). 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 column chromatography (SiO2, methanol/dichloromethane) to afford 3-hydroxy-3-[2-(methylamino)-1H-benzimidazol-5-yl]-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one (3.3 mg). 1H NMR (400 MHz, CD3OD): 7.79 (d, 1H), 7.54-7.48 (m, 2H), 7.29-7.26 (m, 2H), 7.18-7.16 (m, 2H), 7.11-7.01 (m, 4H), 6.86 (dd, 1H), 4.57 (d, 1H), 4.34 (d, 1H), 2.96 (s, 3H); MS (EI) for C23H20N4O2: 385 (MH+).

Workup

  1. temperaturewas cooled to room temperature
  2. custompartitioned with water
  3. additiona mixture of acetonitrile-ethyl acetate (1:9, 200 mL)
  4. washThe organic layer was washed with water and brine
  5. dry with materialthen dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated in vacuo
  8. customThe residue was purified by column chromatography (SiO2, methanol/dichloromethane)

Sources & evidence

ORD record
ord-390339aa18354b3cbed8951a810ac3a2
Source dataset
uspto-grants-2014_04
Patent number
US08697737B2

Reaction notes

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