Sulfuric Acid → HCID 68559381, compound

HRID 19722Notes

Reaction equation

HRID 19722 reaction equation
[NH2:1][C:2]1([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=O.S(=O)(=O)(O)O>C(O)(=O)C.[Pd]>[CH:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[CH2:3][C:2]1([NH2:1])[CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[CH:10]12

Participants

5

Reactant 2

HCID 1118Sulfuric AcidHCID 68559284HCID 68559284, compound

Product 1

HCID 68559381HCID 68559381, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

K3Fe(CN)6 (18.0 g, 54.8 mmol) is added to hot (80° C.) degassed water (150 ml), followed by 2-benzylindan-1-one (J Mol Catal A 2000, 154, 237; 3.8 g, 17.1 mmol). Concentrated aqueous ammonia (14 ml) is then added over 15 minutes and the reaction mixture is heated at 80-90° C. in the dark for 24 hours. After cooling to ambient temperature, the mixture is extracted with chloroform. The combined chloroform extracts are extracted with 3 M HCl and the acidic extracts are evaporated to afford 2-amino-2-benzylindan-1-one hydrochloride salt, MH+238. A suspension of 2-amino-2-benzylindan-1-one (0.506 g, 2.13 mmol) and 10% Pd/C (0.130 g) in acetic acid (15 ml) is hydrogenated at 0.35 bar for 24 hours. Concentrated sulphuric acid (1.5 ml) is added and the reaction is hydrogenated for a further 7 hours. The catalyst is filtered through a Celite™ filter plug and mixture concentrated in vacuo. The residue is basified to pH 8 with saturated aqueous sodium bicarbonate and extracted with ether. The ether extracts are washed with brine, dried (Na2SO4) and evaporated. The crude product is purified by flash chromatography (30:1 CH2Cl2-MeOH elution) to afford 4b,10-dihydro-9H-indeno[1,2-a]inden-9a-ylamine, MH+222. A mixture of 4b,10-dihydro-9H-indeno[1,2-a]inden-9a-ylamine (0.296 g, 1.34 mmol) and R-8-benzyloxy-5-oxiranyl-1H-quinolin-2-one (0.262 g, 0.893 mmol) in 2-methoxyethyl ether (4.5 ml) is heated in a sealed tube at 190° C. for 50 hours. The solvent is evaporated and the crude product purified by preparative LCMS to afford 5-[R-2-(4b,10-dihydro-9H-indeno-[1,2-a]inden-9a-ylamino) 1-hydroxyethyl]-8-benzyloxy-1H-quinolin-2-one, MH+515. A suspension of 5-[R-2-(4b,10-dihydro-9H-indeno[1,2-a]inden-9a-ylamino) 1-hydroxy-ethyl]-8-benzyloxy-1H-quinolin-2-one (10 mg, 0.02 mmol) and 10% Pd/C (8 mg) in ethanol (5 ml) is hydrogenated at 0.35 bar for 30 minutes. The catalyst is filtered through a Celite™ filter plug and the solvent evaporated to afford 5-[R-2-(4b,10-dihydro-9H-indeno[1,2-a]inden-9a-ylamino) 1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one, MH+426.

Workup

  1. waitthe reaction is hydrogenated for a further 7 hours
  2. filtrationThe catalyst is filtered through a Celite™
  3. filtrationfilter plug and mixture
  4. concentrationconcentrated in vacuo
  5. extractionextracted with ether
  6. washThe ether extracts are washed with brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customThe crude product is purified by flash chromatography (30:1 CH2Cl2-MeOH elution)

Sources & evidence

ORD record
ord-40c3399a94ae4fc1be4b2a6c7409b9fe
Source dataset
uspto-grants-2010_06
Patent number
US07745462B2

Reaction notes

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