o-Bis(bromomethyl)benzene → 7-chloro-5,6-dihydro-3-(3-isoindolin-2-yl-methyl-1,2,4-oxadiazol-5-yl)-5-methyl-4H-imidazo[1,5-a][1,4]-benzodiazepin-6-one

HRID 1378049Notes

Reaction equation

HRID 1378049 reaction equation
NC[C:3]1[N:7]=[C:6]([C:8]2[N:9]=[CH:10][N:11]3[C:17]4[CH:18]=[CH:19][CH:20]=[C:21]([Cl:22])[C:16]=4[C:15](=[O:23])[N:14]([CH3:24])[CH2:13][C:12]=23)[O:5][N:4]=1.[CH2:25]([N:27](C(C)C)C(C)C)C.Br[CH2:35][C:36]1[C:37]([CH2:42]Br)=[CH:38][CH:39]=[CH:40][CH:41]=1>CN(C)C=O>[Cl:22][C:21]1[C:16]2[C:15](=[O:23])[N:14]([CH3:24])[CH2:13][C:12]3[N:11]([CH:10]=[N:9][C:8]=3[C:6]3[O:5][N:27]([CH3:25])[CH:3]([N:4]4[CH2:42][C:37]5[C:36](=[CH:41][CH:40]=[CH:39][CH:38]=5)[CH2:35]4)[N:7]=3)[C:17]=2[CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 66665o-Bis(bromomethyl)benzeneHCID 81531DiisopropylethylamineHCID 229142613-(3-aminomethyl-1,2,4-oxadiazol-5-yl)-7-chloro-5,6-dihydro-5-methyl-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one

Product 1

HCID 677133697-chloro-5,6-dihydro-3-(3-isoindolin-2-yl-methyl-1,2,4-oxadiazol-5-yl)-5-methyl-4H-imidazo[1,5-a][1,4]-benzodiazepin-6-oneYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3.44 g (10 mmol) of 3-(3-aminomethyl-1,2,4-oxadiazol-5-yl)-7-chloro-5,6-dihydro-5-methyl-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one, 30 ml of N,N-dimethylformamide, 3.7 ml (22 mmol) of N-ethyldiisopropylamine and 2.9 g (11 mmol) of α,α'-dibromo-o-xylene were stirred at room temperature for 6 hours. After evaporating the solvent the residue was chromatographed on 230 g of silica gel while eluting with ethyl acetate. The uniform fractions were evaporated. There were obtained 1.56 g (35%) of 7-chloro-5,6-dihydro-3-(3-isoindolin-2-yl-methyl-1,2,4-oxadiazol-5-yl)-5-methyl-4H-imidazo[1,5-a][1,4]-benzodiazepin-6-one, which was converted into the hydrochloride of m.p. 180°-184°.

Workup

  1. customAfter evaporating the solvent the residue
  2. customwas chromatographed on 230 g of silica gel
  3. washwhile eluting with ethyl acetate
  4. customThe uniform fractions were evaporated

Sources & evidence

ORD record
ord-7c0b70fa082c40adb5f87b51fc62a103
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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