Dichloromethane → HCID 70078123, compound

HRID 1378024Notes

Reaction equation

HRID 1378024 reaction equation
[NH2:1][CH2:2][C:3]1[O:7][N:6]=[C:5]([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)[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:5]4[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)[O:7][N:6]=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 22914273HCID 22914273, compound

Product 1

HCID 70078123HCID 70078123, compoundYield 26%

Procedure

A suspension of 0.49 g (1.5 mmol) of 3-(5-aminomethyl-1,2,4-oxadiazol-3-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one in 8 ml of methylene chloride was treated under argon with 0.77 ml (4.5 mmol) of N-ethyldiisopropylamine and 0.475 g (1.8 mmol) of α,α'-dibromo-o-xylene and stirred at room temperature under argon for 7 hrs. The solution was washed once with 10 ml of water, dried with sodium sulfate, filtered and evaporated. The crude product was purified by chromatography on 40 g of silica gel (methylene chloride/acetone 4:1, then 22:1), whereupon the eluate was evaporated and the residue was taken up in 3 ml of methanol. The solution was acidified with ethereal hydrochloric acid and the solvent was removed in a vacuum. The residue was dissolved in 3 ml of methanol, whereupon the solution was cooled to about 0° and diluted dropwise with 3 ml of ether. Thereby, white crystals separated slowly and were filtered off. There were obtained 190 mg (26%) of 8-fluoro-3-(5-isoindolin-2-ylmethyl-1,2,4-oxadiazol-3-yl)-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one hydrochloride (22:3) of m.p. 177°-184° (dec.).

Workup

  1. washThe solution was washed once with 10 ml of water
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified by chromatography on 40 g of silica gel (methylene chloride/acetone 4:1
  6. custom22:1), whereupon the eluate was evaporated
  7. customthe solvent was removed in a vacuum
  8. dissolutionThe residue was dissolved in 3 ml of methanol, whereupon the solution
  9. temperaturewas cooled to about 0°
  10. additiondiluted dropwise with 3 ml of ether
  11. customThereby, white crystals separated slowly
  12. filtrationwere filtered off

Sources & evidence

ORD record
ord-8b8564b5ff0548bd8a5a61d82bb677f6
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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