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 380794ノート

反応式

HRID 380794 の反応式
[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

参加物

10

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-8d6562bffd874d7884e285893fa48952
出典データセット
uspto-grants-2001_10
特許番号
US06303783B1

反応ノート

読み込み中…