Ethylenediamine → HCID 66898582, compound

HRID 1521777Notes

Reaction equation

HRID 1521777 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11](COCC[Si](C)(C)C)[N:10]=[C:9]2[O:23][CH3:24].C(N)CN.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[O:3]1[CH2:4][CH2:5][O:1][CH:2]1[C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[C:9]2[O:23][CH3:24]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 2724141Tetrabutylammonium Fluoride2×HCID 58407640HCID 58407640, compound

Product 1

HCID 66898582HCID 66898582, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To 940 mg (2.682 mmol) 5-(1,3-dioxolan-2-yl)-3-methoxy-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole (Example 6A) and 805 mg (13.41 mmol) ethane-1,2-diamine in THF (50 ml) were added 12.98 ml (12.98 mmol) tetrabutylammonium fluoride solution (1.0 M in THF). The reaction mixture was heated to 50° C. for 3 h. After this time, 12.98 ml (12.98 mmol) tetrabutylammonium fluoride solution (1.0 M in THF) were added again, and heating was continued for further 12 h until conversion was complete. The mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The layers were separated, and the aqueous layer was washed twice with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After filtration, the solvent was evaporated, and the remaining solid was purified by chromatography on silica gel (cyclohexane/ethyl acetate gradient) to afford 556 mg (94% of th.) of the intermediate compound 5-(1,3-dioxolan-2-yl)-3-methoxy-1H-indazole [LC-MS (method 3): Rt=1.44 min; MS (ESIpos): m/z=211 (M+H)+]. This material was dissolved in ethanol (37 ml), treated with 1 N hydrochloric acid (9.4 ml) and heated to 90° C. for 30 minutes. After this time, the mixture was evaporated to dryness, and the crude aldehyde thus obtained was used in the next step without further purification.

Workup

  1. temperatureheating
  2. customThe mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  3. customThe layers were separated
  4. washthe aqueous layer was washed twice with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationAfter filtration
  8. customthe solvent was evaporated
  9. customthe remaining solid was purified by chromatography on silica gel (cyclohexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-2ddc9b6b51214f6d98c13e23140b6030
Source dataset
uspto-grants-2015_07
Patent number
US09073939B2

Reaction notes

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