Isopropanol → Isopropyl 9-(2,5-dichlorobenzyl)-9H-beta-carboline-3-carboxylate

HRID 992558Notes

Reaction equation

HRID 992558 reaction equation
C(O)(=O)C.[Cl:5][C:6]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:7]=1[CH2:8][N:9]1[C:21]2[CH:20]=[N:19][C:18]([C:22]([OH:24])=[O:23])=[CH:17][C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2.S(Cl)(Cl)=O.[CH:34](O)([CH3:36])[CH3:35].C(N(CC)CC)C>C(Cl)Cl>[Cl:5][C:6]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:7]=1[CH2:8][N:9]1[C:21]2[CH:20]=[N:19][C:18]([C:22]([O:24][CH:34]([CH3:36])[CH3:35])=[O:23])=[CH:17][C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 697103409-(2,5-dichlorobenzyl)-9H-beta-carboline-3-carboxylic acid acetate salt

Product 1

HCID 9823014Isopropyl 9-(2,5-dichlorobenzyl)-9H-beta-carboline-3-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 9-(2,5-dichlorobenzyl)-9H-β-carboline-3-carboxylic acid acetate salt (1.30 g, 3.02 mmol) and thionyl chloride (2.2 mL, 30 mmol) was stirred and refluxed for 2 hours. The reaction mixture was concentrated in vacuo and the resulting dark oil was used without further purification. The oil was dissolved in 15 mL of DMF (theor. 0.2M). A portion (2.5 mL, 0.5 mmol) of this solution was added to a large excess of isopropanol and triethylamine and the resulting mixture stirred at 60° C. overnight. After cooling to room temperature, the mixture was shaken with methylene chloride, and the mixture was washed with water and brine. The organic phase was dried with anhydrous sodium sulfate and the solvent removed in vacuo. Purification by flash chromatography on silica gel afforded the product as an oil (144 mg, 70%). 1H NMR (300 MHz, DMSO-d6) δ8.80 (s, 1H), 8.75 (s, 1H), 8.13-8.16 (m, 1H), 7.50-7.56 (m, 1H), 7.20-7.33 (m, 3H), 7.08 (dd,J=2.6, 8.7, 1H), 6.48 (d,J=2.3, 1H), 5.48 (s, 2H), 5.37 (septet, J=6.4, 1 H), 1.43 (d, J=6.4, 6H).

Workup

  1. temperaturerefluxed for 2 hours
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe resulting dark oil was used without further purification
  4. dissolutionThe oil was dissolved in 15 mL of DMF (theor. 0.2M)
  5. stirringthe resulting mixture stirred at 60° C. overnight
  6. washthe mixture was washed with water and brine
  7. dry with materialThe organic phase was dried with anhydrous sodium sulfate
  8. customthe solvent removed in vacuo
  9. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-37923ac9320d4da198f9b1a7a95b6ec6
Source dataset
uspto-grants-2002_10
Patent number
US06469021B1

Reaction notes

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