Hydrazine → HCID 10315725, compound

HRID 1349684Notes

Reaction equation

HRID 1349684 reaction equation
[CH3:1][N:2]([CH3:24])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:21]([NH2:23])=O)[CH:19]=3)[NH:14][N:13]=2)=[CH:8][CH:7]=1.COC(OC)[N:28]([CH3:30])C.[NH2:33]N>C(O)(=O)C>[NH:33]1[C:21]([C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[NH:14][N:13]=[C:12]3[C:9]2[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][N:2]([CH3:24])[CH3:1])=[CH:7][CH:8]=2)=[N:23][CH:30]=[N:28]1

Participants

5

Reactant 3

HCID 9321HydrazineHCID 78373Dimethylformamide dimethyl acetalHCID 22480245HCID 22480245, compound

Product 1

HCID 10315725HCID 10315725, compoundYield 86.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
93 °C

Procedure

A mixture of 3-{4-[2-(dimethylamino)ethoxy]phenyl}-1H-indazole-5-carboxamide (79 mg, 0.243 mmol) and N,N-dimethylformamide dimethyl acetal (10.0 mL, 75.3 mmol, 310 equiv.) was heated at 93° C. for 3 h and then concentrated. To the concentrate was added 4.0 mL of glacial acetic acid (AcOH), and anhydrous hydrazine (204 mg, 6.36 mmol, 26.2 equiv.). The mixture was heated at 93° C. for 3 h and concentrated. The residue was partitioned between EtOAc and 6.0 N aq. NaOH and the layers separated. The aqueous layer was extracted with 2×EtOAc and then the pH adjusted between 10–11 with 6.0 N aq. HCl to give maximum cloudiness. The mixture was extracted with 3×EtOAc. The combined organics were dried (Na2SO4), filtered, and concentrated to afford the title compound (73.3 mg, 86.5% yield): 1H NMR (DMSO-d6) δ 14.20 (br s, 1H), 13.30 (br s, 1H), 8.65 (s, 1H), 8.37 (br s, 1H), 8.07 (d, 1H), 7.96 (d, 2H), 7.65 (d, 1H), 7.15 (d, 2H), 4.14 (t, 2H), 2.67 (t, 2H), 2.24 (s, 6H); ES-MS (m/z) 349 [M+1]+.

Workup

  1. concentrationconcentrated
  2. temperatureThe mixture was heated at 93° C. for 3 h
  3. concentrationconcentrated
  4. customThe residue was partitioned between EtOAc and 6.0 N aq. NaOH
  5. customthe layers separated
  6. extractionThe aqueous layer was extracted with 2×EtOAc
  7. customto give maximum cloudiness
  8. extractionThe mixture was extracted with 3×EtOAc
  9. dry with materialThe combined organics were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-9c3b20ba9d8e4504a2a302d27a674870
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

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