Trifluoroacetic acid → (s)-4-(2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylic acid[3-(4-trifluoromethylphenyl)-2-propenyl]amide

HRID 856328ノート

反応式

HRID 856328 の反応式
[CH3:1][C@@:2]1([CH2:13][N:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22]C(C)(C)C)=O)[CH2:16][CH2:15]2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[F:41][C:42]([F:54])([F:53])[C:43]1[CH:48]=[CH:47][C:46]([CH:49]=[CH:50][CH2:51][NH2:52])=[CH:45][CH:44]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>O.CN(C=O)C.C(Cl)Cl>[F:41][C:42]([F:53])([F:54])[C:43]1[CH:44]=[CH:45][C:46]([CH:49]=[CH:50][CH2:51][NH:52][C:20]([N:17]2[CH2:18][CH2:19][N:14]([CH2:13][C@:2]3([CH3:1])[O:6][C:5]4=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]4[CH2:3]3)[CH2:15][CH2:16]2)=[O:22])=[CH:47][CH:48]=1

参加物

9

反応物 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 694813093-(4-Trifluoromethylphenyl)-2-propenylamineHCID 69635111tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate

生成物 1

HCID 69479568(s)-4-(2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylic acid[3-(4-trifluoromethylphenyl)-2-propenyl]amide収率 96.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate prepared in Example 393 (926 mg, 2.52 mmol), trifluoroacetic acid (10 ml) and methylene chloride (3 ml) was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in DMF (3 ml) and neutralized with triethylamine (2 ml, 14.35 mmol). To the solution, a mixture of 3-(4-trifluoromethylphenyl)-2-propenylamine (761 mg, 3.78 mmol), 1,1′-carbonyldiimidazole (613 mg, 3.78 mmol) and DMF (3 ml) stirred at room temperature overnight was added followed by stirring at room temperature overnight. To the reaction mixture, water was added followed by extraction with ethyl acetate. The extract was washed with water three times and a saturated saline solution, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=20/1) to afford (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylic acid[3-(4-trifluoromethylphenyl)-2-propenyl]amide (1.2 g, yield 96%) as a light yellow powder.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (3 ml)
  3. stirringstirred at room temperature overnight
  4. additionwas added
  5. stirringby stirring at room temperature overnight
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe extract was washed with water three times
  8. dry with materiala saturated saline solution, dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=20/1)

出典と根拠

ORDレコード
ord-fad85264a1d9402c8969d5e7524a81ba
出典データセット
uspto-grants-2007_08
特許番号
US07262212B2

反応ノート

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