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

HRID 486200Notes

Reaction equation

HRID 486200 reaction equation
C(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:27])[CH2:24][CH2:25][CH2:26][C:15]=12.[CH3:28][C:29]1[N:30]([C:36]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:31]=[C:32]([CH:34]=[O:35])[N:33]=1.C(O)(=O)C(O)=O>O1CCCC1.CCCCCC.O>[OH:35][CH:34]([C:32]1[N:33]=[C:29]([CH3:28])[N:30]([C:36]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH:31]=1)[CH:24]1[C:23](=[O:27])[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 7912DiisopropylamineHCID 1107438710-methyl-8,9-dihydropyrido[1,2-a]indol-6(7H)-oneHCID 150519362-methyl-1-trityl-1H-imidazole-4-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 150519378,9-dihydro-7-[(hydroxy)(2-methyl-1-trityl-1H-imidazol-4-yl)methyl]-10-methylpyrido[1,2-a]indol-6(7H)-oneYield 74.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

To a solution of diisopropylamine (557 mg) in tetrahydrofuran (7.5 ml) at -70° C. under a nitrogen atmosphere was added 1.64M butyllithium in hexane (3.35 ml). After being stirred at the same temperature for 20 minutes, the mixture was treated with a solution of 8,9-dihydro-10-methylpyrido[1,2-a]indol-6(7H)-one (995 mg) in tetrahydrofuran (10 ml) over 15 minutes. The mixture was stirred at -70° C. for 40 minutes, and a solution of 2-methyl-1-trityl-1H-imidazole-4-carbaldehyde (1.76 g) in tetrahydrofuran (20 ml) was added dropwise over 15 minutes. After the mixture was stirred at -70° C. for 1 hour and at ambient temperature for 1 hour, it was diluted with water and neutralized with a aqueous solution of oxalic acid. The organic layer was separated and the aqueous layer was extracted with chloroform. The organic layers were combined and washed with brine and dried over anhydrous magnesium sulfate. After the solvent was evaporated in vacuo, the residue was subjected to a column chromatography on silica gel (20% ethyl acetate-chloroform). The fractions containing the product were combined and evaporated in vacuo. The residue was crystallized from n-hexane-ether to give 8,9-dihydro-7-[(hydroxy)(2-methyl-1-trityl-1H-imidazol-4-yl)methyl]-10-methylpyrido[1,2-a]indol-6(7H)-one (2.06 g).

Workup

  1. stirringThe mixture was stirred at -70° C. for 40 minutes
  2. stirringAfter the mixture was stirred at -70° C. for 1 hour and at ambient temperature for 1 hour
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with chloroform
  5. washwashed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customAfter the solvent was evaporated in vacuo
  8. additionThe fractions containing the product
  9. customevaporated in vacuo
  10. customThe residue was crystallized from n-hexane-ether

Sources & evidence

ORD record
ord-05191a0db0cc4698bc8315c44431c35c
Source dataset
uspto-grants-1994_03
Patent number
US05290785

Reaction notes

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