Acetohydrazide → 8-Bromo-1-methyl-5,6-dihydrospiro[benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine-4,1'-cyclopropane]

HRID 1485431Notes

Reaction equation

HRID 1485431 reaction equation
[Br:1][C:2]1[CH:15]=[CH:14][C:5]2[NH:6][C:7](=S)[C:8]3([CH2:11][NH:12][C:4]=2[CH:3]=1)[CH2:10][CH2:9]3.[C:16]([NH:19][NH2:20])(=O)[CH3:17]>C(O)CCC>[Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]3[C:16]([CH3:17])=[N:19][N:20]=[C:7]3[C:8]3([CH2:10][CH2:9]3)[CH2:11][NH:12][C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 14039AcetohydrazideHCID 867185037-bromo-4,5-dihydrospiro[benzo[b][1,4]diazepine-3,1'-cyclopropane]-2(1H)-thione

Product 1

HCID 709790438-Bromo-1-methyl-5,6-dihydrospiro[benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine-4,1'-cyclopropane]Yield 53%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 7-bromo-4,5-dihydrospiro[benzo[b][1,4]diazepine-3,1′-cyclopropane]-2(1H)-thione (500 mg, 1.77 mmol) and acetohydrazide (1.05 g, 14.2 mmol) in n-butanol (15 mL) was heated to 130° C., and maintained at the same temperature for 12 hours. The reaction mixture was concentrated, extracted with ethyl acetate (15 mL), washed with water (25 mL*2). The organic phase was separated, dried by sodium sulfate, filtered and concentrated to give the crude product, which was purified by column chromatography (silica gel, dichloromethane/methanol=30:1) to afford 8-bromo-1-methyl-5,6-dihydrospiro[benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine-4,1′-cyclopropane] (286 mg, 53%). 1H NMR (300 MHz, d6-DMSO): δ 7.31-7.28 (m, 2H), 7.11 (dd, J=6.0 Hz, J=2.4 Hz, 1H), 5.80-5.78 (m, 1H), 3.36-3.35 (m, 2H), 2.37 (s, 3H), 0.88-0.86 (m, 2H), 0.77-0.73 (m, 2H). LRMS (M+H)+: calcd 304.03. found 304.

Workup

  1. temperaturemaintained at the same temperature for 12 hours
  2. concentrationThe reaction mixture was concentrated
  3. extractionextracted with ethyl acetate (15 mL)
  4. washwashed with water (25 mL*2)
  5. customThe organic phase was separated
  6. dry with materialdried by sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product, which
  10. customwas purified by column chromatography (silica gel, dichloromethane/methanol=30:1)

Sources & evidence

ORD record
ord-e846924cc00d40c79edac708d3a55578
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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