L-Alanine → 2-{{2-Chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluoro-phenyl}imino}-alpha-methyl-4-oxo-3-thiazolidineacetic acid

HRID 380794Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 380794
[NH2:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3].C1C=C2[CH:13]([CH2:20][O:21]C(NCC=O)=O)C3C(C2=CC=1)=CC=CC=3.N1CCCCC1.[Cl:34][C:35]1[CH:40]=[C:39]([F:41])[C:38]([N:42]2[C:47](=[O:48])[CH:46]=[C:45]([C:49]([F:52])([F:51])[F:50])[N:44]([CH3:53])[C:43]2=[O:54])=[CH:37][C:36]=1[N:55]=[C:56]=[S:57].BrCC(OC)=O.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(Cl)Cl.CO>[Cl:34][C:35]1[CH:40]=[C:39]([F:41])[C:38]([N:42]2[C:47](=[O:48])[CH:46]=[C:45]([C:49]([F:50])([F:51])[F:52])[N:44]([CH3:53])[C:43]2=[O:54])=[CH:37][C:36]=1[N:55]=[C:56]1[N:1]([CH:2]([CH3:3])[C:4]([OH:6])=[O:5])[C:20](=[O:21])[CH2:13][S:57]1

Komponenten

10

Edukt 6

HCID 5950L-AlanineHCID 8082PiperidineHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 10858926(9H-Fluoren-9-yl)methyl 2-oxoethylcarbamateHCID 183659632-Chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluoro-phenyl isothiocyanate

Produkt 1

HCID 183659022-{{2-Chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluoro-phenyl}imino}-alpha-methyl-4-oxo-3-thiazolidineacetic acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

An alanine substituted resin (1.0 mmol) which is N-protected with Fmoc and supported on polystyrene (commercially available as Fmoc-gly-Wang resin from Midwest Bio-tech Inc., Fishers, Ind.) is treated with a 20% piperdine in N,N-dimethylformamide solution to remove the Fmoc protecting group. The solvents are removed and the resin is washed with N,N-dimethylformamide, methanol and methylene chloride, treated with a solution of 2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluorophenyl isothiocyanate (0.57 g, 1.5 mmol) in methylene chloride, and stirred at room temperature for 6 hours. The solvents are removed and the resin is washed with N,N-dimethylformamide, methanol and methylene chloride, diluted with N,N-dimethylformamide, treated with methyl bromoacetate (0.46 g, 3 mmol) and N,N-diisopropylethylamine (1 ml), and stirred overnight at room temperature. The solvents are removed and the resultant resin is washed sequentially with N,N-dimethylformamide, methanol and methylene chloride, air-dried, and cleaved with trifluoroacetic acid. Column chromatography of the resultant reaction mixture using silica gel and a 15% methanol in methylene chloride solution gives the title product (0.55 g) which is identified by 1H and 13C NMR spectral analyses.

Aufarbeitung

  1. customto remove the Fmoc protecting group
  2. customThe solvents are removed
  3. washthe resin is washed with N,N-dimethylformamide, methanol and methylene chloride
  4. customThe solvents are removed
  5. washthe resin is washed with N,N-dimethylformamide, methanol and methylene chloride
  6. additiondiluted with N,N-dimethylformamide
  7. stirringstirred overnight at room temperature
  8. customThe solvents are removed
  9. washthe resultant resin is washed sequentially with N,N-dimethylformamide, methanol and methylene chloride
  10. customair-dried
  11. customColumn chromatography of the resultant reaction mixture

Quellen und Nachweise

ORD-Eintrag
ord-8d6562bffd874d7884e285893fa48952
Quelldatensatz
uspto-grants-2001_10
Patentnummer
US06303783B1

Notizen zur Reaktion

Wird geladen…