Lithium Hexamethyldisilazide → Ethyl 3-[2-butyl-3,4-dihydro-4-oxo-3-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-6-quinazolinyl]-2-propenoate

HRID 1708474Notes

Reaction equation

HRID 1708474 reaction equation
[CH2:1]([C:5]1[NH:6][C:7]2[C:12]([C:13](=[O:15])[N:14]=1)=[CH:11][C:10]([CH:16]=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH3:4].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=2[C:47]2[N:51]([C:52]([C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)([C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=3)[C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[N:50]=[N:49][N:48]=2)=[CH:37][CH:36]=1>O1CCCC1.C(OCC)(=O)C>[CH2:1]([C:5]1[N:14]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=3[C:47]3[N:51]([C:52]([C:65]4[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=4)([C:59]4[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=4)[C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[N:50]=[N:49][N:48]=3)=[CH:39][CH:40]=2)[C:13](=[O:15])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH:16]=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:11]=2)[N:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 100534615-(4'-(Bromomethyl)(1,1'-biphenyl)-2-yl)-1-trityl-1H-tetraazoleHCID 178441843HCID 178441843, compound

Product 1

HCID 54221423Ethyl 3-[2-butyl-3,4-dihydro-4-oxo-3-[[2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]methyl]-6-quinazolinyl]-2-propenoateYield 38.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 1.75 g of ethyl 3-(2-butyl-1,4-dihydro-4-oxo-6-quinazolinyl)-2-propenoate in 25 ml of dry tetrahydrofuran at room temperature is rapidly added 6.70 g of a 1.0M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran. After stirring for 20 minutes at room temperature 3.899 g of 5-(4'-(bromomethyl)-[1,1'-biphenyl]-2-yl]-1-(triphenylmethyl)-1H-tetrazole is rapidly added in one portion and the reaction mixture heated at reflux for 48 hours. After cooling to room temperature, the reaction mixture is diluted with ethyl acetate and the organic layer washed with 5% HCl, water and brine. The organic layer is dried with MgSO4 and concentrated in vacuo to a residue which is purified by column chromatography on silica gel by eluting with 1:4 ethyl acetate-hexanes to give 1.732 g of the desired product as a solid. FAB mass spec 799 (M+Na).

Workup

  1. additionis rapidly added in one portion
  2. temperaturethe reaction mixture heated
  3. temperatureat reflux for 48 hours
  4. washthe organic layer washed with 5% HCl, water and brine
  5. dry with materialThe organic layer is dried with MgSO4
  6. concentrationconcentrated in vacuo to a residue which
  7. customis purified by column chromatography on silica gel
  8. washby eluting with 1:4 ethyl acetate-hexanes

Sources & evidence

ORD record
ord-436c1628b617403c98e37b43a2f1e22f
Source dataset
uspto-grants-1994_10
Patent number
US05358951

Reaction notes

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