Acetohydrazide → 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepine

HRID 1485423Notes

Reaction equation

HRID 1485423 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]2[NH:6][C:7](=S)[CH:8](C)[CH2:9][NH:10][C:4]=2[CH:3]=1.[C:15]([NH:18][NH2:19])(=O)C>C(O)CCC>[CH:15]1[N:6]2[C:5]3[CH:13]=[CH:14][CH:2]=[CH:3][C:4]=3[N:10]=[CH:9][CH2:8][C:7]2=[N:19][N:18]=1

Participants

4

Reactant 2

HCID 14039AcetohydrazideHCID 867185007-bromo-3-methyl-4,5-dihydro-1H-benzo[b][1,4]diazepine-2(3H)-thione

Product 1

HCID 867185014H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepine

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 7-bromo-3-methyl-4,5-dihydro-1H-benzo[b][1,4]diazepine-2(3H)-thione (1.5 g, 5.5 mmol) and acetohydrazide (693 mg, 9.36 mmol) in n-butanol (20 mL) was heated at 130° C. for 12 hours. The reaction mixture was concentrated in vacuo, diluted with water (20 mL), extracted with ethyl acetate (15 mL×3) and washed with brine (10 mL×3). The combined organic phase was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated to give a crude product, which was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to afford 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepine, 5,6-dihydro-1,4-dimethyl-8-bromo as a white solid (1 g, 62%). 1H NMR (300 MHz, CDC13): δ 7.19-7.14 (m, 2H), 7.01 (d, J=8.1 Hz, 1H), 3.74-3.64 (m, 1H), 3.43-3.36 (m, 1H), 3.13-3.05 (m, 1H), 2.49 (s, 3H), 1.50 (d, J=6.9 Hz, 3H). LRMS (M+H)+: calcd 292.03. found 292.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with water (20 mL)
  3. extractionextracted with ethyl acetate (15 mL×3)
  4. washwashed with brine (10 mL×3)
  5. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. customto give a crude product, which
  9. customwas purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-ed89a122755e4596bbb7cba8bdc5f28c
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

Loading…