Hydrazine hydrate (1:1) → 1240518-37-9

HRID 1892920Notes

Reaction equation

HRID 1892920 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH3:23])=[C:6]2[C:10]=1[NH:9][N:8]=[C:7]2[N:11]1C(=O)C2C(=CC=CC=2)C1=O.O.NN>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH3:23])=[C:6]2[C:10]=1[NH:9][N:8]=[C:7]2[NH2:11]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58054480HCID 58054480, compound

Product 1

HCID 580544601240518-37-9Yield 60%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 2-[7-fluoro-4-(methyloxy)-1H-indazol-3-yl]-1H-isoindole-1,3(2H)-dione (for a preparation see Intermediate 13) (1.36 g, 4.37 mmol) in ethanol (15 mL) at 0° C. (ice/water bath) was added hydrazine hydrate (0.638 mL, 13.11 mmol) dropwise. The ice/water bath was removed and the reaction mixture was allowed to warm to room temperature. Stirring was continued for a further 40 min. During this time the reaction mixture became very viscous. Acetone (10 mL) was added to the reaction and the resultant reaction mixture was allowed to stand at room temperature overnight. The solid was removed by filtration and washed with acetone (×2). The combined filtrates were concentrated in vacuo. The solid was triturated in cyclohexane-ethyl acetate (2:1; ˜25 mL) and then collected by filtration to give the title compound (479 mg, 60%) as a light brown powder. LCMS (System A) RT=0.69 min, ES+ve m/z 182 (M+H)+. The filtrate was concentrated and the resultant oil was loaded in dichloromethane (and minimum amount of methanol) to a silica cartridge 70 g and purified by chromatography on Flashmaster eluting with a 0-50% ethyl acetate-cyclohexane over 30 min. The appropriate fractions were combined and evaporated in vacuo to give another batch of the required product (316 mg, 40%) as a brown oil. LCMS (System A) RT=0.62 min, ES+ve m/z 182 (M+H)+.

Workup

  1. customat 0° C.
  2. customThe ice/water bath was removed
  3. additionAcetone (10 mL) was added to the reaction
  4. customthe resultant reaction mixture
  5. waitto stand at room temperature overnight
  6. customThe solid was removed by filtration
  7. washwashed with acetone (×2)
  8. concentrationThe combined filtrates were concentrated in vacuo
  9. customThe solid was triturated in cyclohexane-ethyl acetate (2:1; ˜25 mL)
  10. filtrationcollected by filtration

Sources & evidence

ORD record
ord-743849928a7e420cba6329108de26fc3
Source dataset
uspto-grants-2013_08
Patent number
US08507543B2

Reaction notes

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