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

HRID 847521Notes

Reaction equation

HRID 847521 reaction equation
[CH:1](NC(C)C)([CH3:3])[CH3:2].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.C(Br)C=C>O1CCCC1.CCCCCC>[CH2:3]([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)[CH:1]=[CH2:2]

Participants

7

Reactant 4

HCID 7841Allyl bromideHCID 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 104607697-allyl-8,9-dihydro-10-methyl-7-[(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-oneYield 66.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

To a solution of diisopropylamine (395 mg) in tetrahydrofuran (5 ml) at -70° C. under a nitrogen atmosphere was added 1.64 M butyllithium in hexane (2.62 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 (1.61 g) in tetrahydrofuran (5 ml) over 15 minutes. The mixture was stirred at -65° C. for 30 minutes and at -30~-40° C. for 30 minutes and a solution of allyl bromide (363 mg) in tetrahydrofuran (5 ml) was added dropwise at -65° C. over 10 minutes. After the mixture was stirred at -65° C. for 1 hour, at -20° C. for 1 hour and at ambient temperature for 1 hour. The resultant mixture was washed with water (10 ml ×2) and brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. Purification of the residue with silica gel column chromatography (5% ethyl acetate-chloroform) gave 7-allyl-8,9-dihydro-10 -methyl-7-[(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one (1.15 g).

Workup

  1. stirringThe mixture was stirred at -65° C. for 30 minutes and at -30~-40° C. for 30 minutes
  2. stirringAfter the mixture was stirred at -65° C. for 1 hour, at -20° C. for 1 hour and at ambient temperature for 1 hour
  3. washThe resultant mixture was washed with water (10 ml ×2) and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customevaporated in vacuo
  6. customPurification of the residue with silica gel column chromatography (5% ethyl acetate-chloroform)

Sources & evidence

ORD record
ord-45027e0d47694192bfe4acaf72a24b93
Source dataset
uspto-grants-1992_08
Patent number
US05141945

Reaction notes

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