Dichloromethane → HCID 70077018, compound

HRID 1378059Notes

Reaction equation

HRID 1378059 reaction equation
[NH2:1][CH2:2][C:3]1[N:7]=[C:6]([C:8]2[N:9]=[CH:10][N:11]3[C:17]4[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=4[C:15](=[O:23])[N:14]([CH3:24])[CH2:13][C:12]=23)[O:5][N:4]=1.C(N(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.C(Cl)[Cl:45]>>[ClH:45].[F:22][C:20]1[CH:19]=[CH:18][C:17]2[N:11]3[CH:10]=[N:9][C:8]([C:6]4[O:5][N:4]=[C:3]([CH2:2][N:1]5[CH2:42][C:37]6[C:36](=[CH:41][CH:40]=[CH:39][CH:38]=6)[CH2:35]5)[N:7]=4)=[C:12]3[CH2:13][N:14]([CH3:24])[C:15](=[O:23])[C:16]=2[CH:21]=1

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 66665o-Bis(bromomethyl)benzeneHCID 81531DiisopropylethylamineHCID 22914303HCID 22914303, compound

Product 1

HCID 70077018HCID 70077018, compoundYield 32%

Procedure

A suspension of 328 mg (1.0 mmol) of 3-(3-aminomethyl-1,2,4-oxadiazol-5-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one in 5 ml of methylene chloride was treated under argon with 0.38 ml (2.2 mmol) of N-ethyldiisopropylamine and 317 mg (1.2 mmol) of α,α'-dibromo-o-xylene and stirred at room temperature under argon for 5 hrs. The solution was washed once with 5 ml of water, dried with sodium sulfate, filtered and evaporated. The crude product was purified by chromatography on 30 g of silica gel (methylene chloride/acetone 4:1, then 2:1). The eluates were evaporated and the residue was taken up in 2.5 ml of methanol. The solution was acidified with ethereal hydrochloric acid and the solvent was removed in a vacuum. The residue was taken up in 6 ml of hot methanol; then cooled to about 0° and the white crystals were isolated by suction filtration. There were obtained 150 mg (32%) of 8-fluoro-3-(3-isoindolin-2-ylmethyl-1,2,4-oxadiazol-5-yl)-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one hydrochloride (1:1) of m.p. 229°-233° (dec.).

Workup

  1. washThe solution was washed once with 5 ml of water
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified by chromatography on 30 g of silica gel (methylene chloride/acetone 4:1
  6. customThe eluates were evaporated
  7. customthe solvent was removed in a vacuum
  8. temperaturethen cooled to about 0°
  9. customthe white crystals were isolated by suction filtration

Sources & evidence

ORD record
ord-89f27428facc4bd6aa4deebf20cbab12
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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