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

HRID 486191Notes

Reaction equation

HRID 486191 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[C:16]1[CH2:25][CH2:24][CH2:23][C:22](=[O:26])[N:17]12.[CH3:27][C:28]1[N:32]([C:33]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:31]=[N:30][C:29]=1[CH:52]=[O:53].C(O)(=O)C(O)=O>O1CCCC1.CCCCCC.O>[OH:53][CH:52]([C:29]1[N:30]=[CH:31][N:32]([C:33]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:28]=1[CH3:27])[CH:23]1[C:22](=[O:26])[N:17]2[C:18]3[C:14]([CH:15]=[C:16]2[CH2:25][CH2:24]1)=[CH:13][CH:21]=[CH:20][CH:19]=3

Participants

9

Reactant 5

HCID 971Oxalic AcidHCID 7912DiisopropylamineHCID 110845538,9-dihydropyrido[1,2-a]indol-6(7H)-oneHCID 118243385-methyl-1-trityl-1H-imidazole-4-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 117569938,9-dihydro-7-[(hydroxy)(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-oneYield 63.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

To a solution of diisopropylamine (658 mg) in tetrahydrofuran (8 ml) at -70° C. under nitrogen atmosphere was added 1.64M butyllithium in hexane (3.96 ml). After being stirred at the same temperature for 20 minutes, the mixture was treated with a solution of 8,9-dihydropyrido[1,2-a]indol-6(7H)-one (1.21 g) in tetrahydrofuran (12 ml) over 15 minutes. The mixture was stirred at -70° C. for 30 minutes, and a solution of 5-methyl-1-trityl-1H-imidazole-4-carbaldehyde (2.29 g) in tetrahydrofuran (20 ml) was added dropwise over 20 minutes. After the mixture was stirred at -70° C. for further 60 minutes and at ambient temperature for 2 hours, it was diluted with water and neutralized with an aqueous solution of oxalic acid. Separated organic layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo to give 8,9-dihydro-7-[(hydroxy)(5methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one (2.21 g) as an amorphous powder. The product was a mixture of two diastereoisomers.

Workup

  1. stirringThe mixture was stirred at -70° C. for 30 minutes
  2. stirringAfter the mixture was stirred at -70° C. for further 60 minutes and at ambient temperature for 2 hours
  3. washSeparated organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-3dd39a1c54834d76a9bde2723d2d773e
Source dataset
uspto-grants-1994_03
Patent number
US05290785

Reaction notes

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