Oxalic Acid → 8,9-dihydro-7,10-dimethyl-7-[(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one

HRID 1681725Notes

Reaction equation

HRID 1681725 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]2[C:23](=[O:53])[CH:24]([CH2:27][C:28]3[N:29]=[CH:30][N:31]([C:34]([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:32]=3[CH3:33])[CH2:25][CH2:26][C:15]=12.CI.C(O)(=O)C(O)=O>O1CCCC1.CCCCCC.O>[CH3:1][C:24]1([CH2:27][C:28]2[N:29]=[CH:30][N:31]([C:34]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)([C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:32]=2[CH3:33])[C:23](=[O:53])[N:16]2[C:17]3[C:22]([C:14]([CH3:13])=[C:15]2[CH2:26][CH2:25]1)=[CH:21][CH:20]=[CH:19][CH:18]=3

Participants

9

Reactant 5

HCID 971Oxalic AcidHCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 100528838,9-dihydro-10-methyl-7-[(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]-pyrido[1,2-a]indol-6(7H)-oneHCID 178418339Butyllithium

Product 1

HCID 100532708,9-dihydro-7,10-dimethyl-7-[(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-oneYield 66.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

To a solution of diisopropylamine (263 mg) in tetrahydrofuran (3 ml) at -70° C. under a nitrogen atmosphere was added 1.64M butyllithium in hexane (1.75 ml). After being stirred at the same temperature for 20 minutes, the mixture was treated with a solution of 8,9-dihydro-10-methyl-7-[(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one (1.07 g) in tetrahydrofuran (5 ml) over 15 minutes. The mixture was stirred at -65° C. for 30 minutes and at -25° C. for 40 minutes and a solution of methyl iodide (282 mg) in tetrahydrofuran (3 ml) was added dropwise at -65° C. over 10 minutes. After the mixture was stirred at -65° C. for 30 minutes and at -20° C. for 1 hour, it was diluted with water and neutralized with an aqueous solution of oxalic acid. The resultant mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo. Purification of the residue with silica gel column chromatography (5% ethyl acetate-chloroform) gave 8,9-dihydro-7,10-dimethyl-7-[(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one (0.73 g).

Workup

  1. stirringThe mixture was stirred at -65° C. for 30 minutes and at -25° C. for 40 minutes
  2. stirringAfter the mixture was stirred at -65° C. for 30 minutes and at -20° C. for 1 hour
  3. extractionThe resultant mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated in vacuo
  7. customPurification of the residue with silica gel column chromatography (5% ethyl acetate-chloroform)

Sources & evidence

ORD record
ord-ba8a51746d4c4b99a0335be207626a3e
Source dataset
uspto-grants-1992_12
Patent number
US05173493

Reaction notes

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