Acetohydrazide → HCID 70978986, compound

HRID 1485380Notes

Reaction equation

HRID 1485380 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2C(=O)[C:13]([CH3:17])([CH3:16])[C:12](=O)[NH:11][C:10]3[CH:19]=[CH:20][CH:21]=[CH:22][C:9]2=3)=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].P(Cl)(=O)([O:32][CH3:33])OC.[C:36]([NH:39][NH2:40])(=O)[CH3:37]>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:33](=[O:32])[C:13]([CH3:16])([CH3:17])[C:12]3=[N:40][N:39]=[C:36]([CH3:37])[N:11]3[C:10]3[CH:19]=[CH:20][CH:21]=[CH:22][C:9]2=3)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 14039AcetohydrazideHCID 101863Phosphorochloridic acid, dimethyl esterHCID 23665647Potassium tert-butoxideHCID 70979050HCID 70979050, compound

Product 1

HCID 70978986HCID 70978986, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(4-chlorophenyl)-3,3-dimethyl-1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione (100 mg, 0.32 mmol) in THF (10 mL) was added a solution of t-BuOK (35.8 mg, 0.32 mmol) dropwise at −78° C. over 10 min. The solution was slowly warmed up to 0° C. in 30 min and recooled to −78° C. for the addition of dimethyl phosphorochloridate (55 mg, 0.38 mmol). The mixture was warmed up to 0° C. over 30 min and stirred for 1 hour at room temperature. The solution was cooled to −78° C. and a solution of acetohydrazide (28 mg, 0.38 mmol) in THF (5 mL) was added. The mixture was heated to reflux for 3 hours. The crude solution was diluted with water (20 mL) and extracted with ethyl acetate (20 mL*3). The combined organic layers were dried over Na2SO4, concentrated in vacuo and the residue was purified by column chromatography (silica-gel, DCM: methanol=20:1) to give 6-(4-chlorophenyl)-1,4,4-trimethyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-one as a white solid (51 mg, yield 44%) LRMS (M+H+) m/z: calcd 352.11. found 352.

Workup

  1. temperatureThe mixture was warmed up to 0° C. over 30 min
  2. temperatureThe solution was cooled to −78° C.
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 3 hours
  5. extractionextracted with ethyl acetate (20 mL*3)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customthe residue was purified by column chromatography (silica-gel, DCM: methanol=20:1)

Sources & evidence

ORD record
ord-6247aa20a9f74260b7de9a774801a69c
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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