Ethylenediamine → HCID 25017296, compound

HRID 422084Notes

Reaction equation

HRID 422084 reaction equation
[CH2:1]([NH2:4])[CH2:2][NH2:3].C[Al](C)C.CO[C:11](=O)[CH2:12][N:13]1[C:21]2[C:16](=[CH:17][C:18]([N:22]3[CH:27]=[CH:26][C:25]4[O:28][C:29]([C:31]5[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=5)=[CH:30][C:24]=4[C:23]3=[O:38])=[CH:19][CH:20]=2)[CH:15]=[N:14]1>C1(C)C=CC=CC=1.O>[Cl:37][C:34]1[CH:35]=[CH:36][C:31]([C:29]2[O:28][C:25]3[CH:26]=[CH:27][N:22]([C:18]4[CH:17]=[C:16]5[C:21](=[CH:20][CH:19]=4)[N:13]([CH2:12][C:11]4[NH:3][CH2:2][CH2:1][N:4]=4)[N:14]=[CH:15]5)[C:23](=[O:38])[C:24]=3[CH:30]=2)=[CH:32][CH:33]=1

Participants

6

Reactant 3

HCID 3301EthylenediamineHCID 16682925TrimethylaluminumHCID 66672822HCID 66672822, compound

Product 1

HCID 25017296HCID 25017296, compoundYield 21.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of ethylenediamine (68 mL, 1.0 mmol) in toluene (0.36 mL) was slowly added trimethyl aluminium (0.50 mL, 10 M in toluene) over ten minutes. The solution was allowed to stir at 0° C. for 5 minutes; then a suspension of methyl-2-(5-(2-(4-chlorophenyl)-4-oxofuro[3,2-c]pyridin-5(4H)-yl)-1H-indazol-1-yl)acetate (0.22 g, 0.50 mmol) in toluene (7.27 mL) was added and the reaction mixture was heated to reflux. The reaction mixture was stirred at reflux for 18 h; then the reaction mixture was diluted with H2O (2 mL) and the solids were removed by filtration. The filtrate was extracted with CH2Cl2 (3×20 mL) and the extracts were dried (Na2SO4), filtered and concentrated. Purification by flash chromatography (silica gel, CH2Cl2/9:1 EtOH with NH4OH, 100:0 to 90:10) yielded the title compound (47.6 mg, 21%) as an off-white solid: 1H NMR (500 MHz, DMSO-d6) δ 8.15 (s, 1H), 7.91 (d, J=9.0 Hz, 1H), 7.83 (d, J=1.5 Hz, 1H), 7.74 (d, J=9.0 Hz, 1H), 7.69 (d, J=7.5 Hz, 1H), 7.64 (s, 1H), 7.57-7.55 (m, 2H), 7.42 (dd, J=9.0, 2.0 Hz, 2H), 6.89 (d, J=7.0 Hz, 1H), 5.21 (s, 2H) 3.51 (br s, 1H), 3.30 (s, 4H); ESI MS m/z 444 [M+H]+; HPLC (Method A) 95.7% (AUC), tR=15.8 min.

Workup

  1. customTo a 0° C.
  2. customover ten minutes
  3. additionwas added
  4. temperaturethe reaction mixture was heated to reflux
  5. stirringThe reaction mixture was stirred
  6. temperatureat reflux for 18 h
  7. customthe solids were removed by filtration
  8. extractionThe filtrate was extracted with CH2Cl2 (3×20 mL)
  9. dry with materialthe extracts were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by flash chromatography (silica gel, CH2Cl2/9:1 EtOH with NH4OH, 100:0 to 90:10)

Sources & evidence

ORD record
ord-d00014a16bbc434390eec8c64626d975
Source dataset
uspto-grants-2012_01
Patent number
US08101632B2

Reaction notes

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