Hydrazine hydrate (1:1) → HCID 178511278, compound

HRID 1852542Notes

Reaction equation

HRID 1852542 reaction equation
O.NN.[N:4]1([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C@H:20]3[CH2:25][CH2:24][C@H:23]([CH2:26][N:27]4C(=O)C5C(=CC=CC=5)C4=O)[CH2:22][CH2:21]3)[N:14]=2)[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]=[N:5]1>CCO>[NH2:27][CH2:26][C@H:23]1[CH2:22][CH2:21][C@H:20]([NH:19][C:15]2[N:14]=[C:13]([N:4]3[C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=4[N:6]=[N:5]3)[CH:18]=[CH:17][N:16]=2)[CH2:25][CH2:24]1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)2×HCID 178515001HCID 178515001, compound

Product 1

HCID 178511278HCID 178511278, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

Hydrazine monohydrate (0.28 mL, 2.7 eq) was added to a solution of trans-2-[4-(4-benzotriazol-1-yl-pyrimidin-2-ylamino)-cyclohexylmethyl]-isoindole-1,3-dione (976 mg, 1 equivalent) in EtOH (60 mL). The reaction mixture was stirred overnight at 70° C., a second aliquot of hydrazine monohydrate (0.22 mL, 2.0 eq) was then added and the mixture was stirred at reflux for 7 hours. The solvent was then evaporated under reduced pressure, the residue was dissolved in a mixture of isopropanol and chloroform and it was acidified until pH 3 by the addition of HCl (1 M). The organic phase was washed 3 times with water. The aqueous phase was basified to pH 8-9 by the addition of NaOH (1 M) and it was extracted 5 times with a mixture of isopropanol and chloroform. The combined organic extracts were dried over Na2SO4, filtered and the solvent was evaporated under reduced pressure. This acid/base extraction procedure was repeated 3 times in order to remove phthalazinone. trans-(4-Aminomethyl-cyclohexyl)-(4-benzotriazol-1-yl-pyrimidin-2-yl)-amine was obtained in 71% purity (450 mg, 65% yield). 1H NMR (400 MHz, CD3OD) δ ppm 8.53-8.85 (1 H, bd), 8.40 (1 H, d, J=5.50 Hz), 8.09 (1 H, d, J=8.31 Hz), 7.67 (1 H, m), 7.53 (1 H, m), 7.39 (1 H, d, J=5.50 Hz), 3.76-3.89 (1 H, m), 2.60 (2 H, d, J=6.60 Hz), 2.11-2.28 (2 H, m), 1.88-2.02 (2 H, m), 1.08-1.54 (5 H, m).

Workup

  1. stirringthe mixture was stirred
  2. temperatureat reflux for 7 hours
  3. customThe solvent was then evaporated under reduced pressure
  4. dissolutionthe residue was dissolved in a mixture of isopropanol and chloroform and it
  5. additionwas acidified until pH 3 by the addition of HCl (1 M)
  6. washThe organic phase was washed 3 times with water
  7. additionThe aqueous phase was basified to pH 8-9 by the addition of NaOH (1 M) and it
  8. extractionwas extracted 5 times
  9. additionwith a mixture of isopropanol and chloroform
  10. dry with materialThe combined organic extracts were dried over Na2SO4
  11. filtrationfiltered
  12. customthe solvent was evaporated under reduced pressure
  13. extractionThis acid/base extraction procedure
  14. customto remove phthalazinone

Sources & evidence

ORD record
ord-48cbbfc56b9149cf8cf2a0ea734d768f
Source dataset
uspto-grants-2015_02
Patent number
US08962622B2

Reaction notes

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