Propargyl alcohol → 2-Amino-5-[4-(difluoromethoxy)phenyl]-5-[3-(4-hydroxybut-1-yn-1-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one

HRID 30575

反応式

HRID 30575 の反応式
[C:1](P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(NC(C)C)(C)C.[NH2:21][C:22]1[N:26]([CH3:27])[C:25](=[O:28])[C:24]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41](Br)[CH:40]=2)([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH:36]([F:38])[F:37])=[CH:31][CH:30]=2)[N:23]=1.[OH:46][CH2:47][C:48]#[CH:49]>O1CCOCC1.[Cu](I)I.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.O>[NH2:21][C:22]1[N:26]([CH3:27])[C:25](=[O:28])[C:24]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH:36]([F:38])[F:37])=[CH:31][CH:30]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([C:1]#[C:49][CH2:48][CH2:47][OH:46])[CH:40]=2)[N:23]=1

参加物

9

反応物 4

HCID 7859Propargyl alcoholHCID 7912DiisopropylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 597903072-amino-4-(3-bromophenyl)-4-(4-(difluoromethoxy)phenyl)-1-methyl-1H-imidazol-5(4H)-one

生成物 1

HCID 161141522-Amino-5-[4-(difluoromethoxy)phenyl]-5-[3-(4-hydroxybut-1-yn-1-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one収率 48%

試薬・触媒・溶媒 4

HCID 83717Copper iodide触媒HCID 498840Bis(benzonitrile)palladium chloride触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
35 °C

実験手順

A mixture of copper iodide (8 mg, 0.04 mmol), bis(benzonitrile)dichloro palladium(II) (23 mg, 0.06 mmol) and anhydrous dioxane under argon was stirred for 3 min., treated with tri-t-butyl phosphine (10% in hexane) (240 mg, 0.12 mmol), stirred for 5 min. treated with diisopropyl amine (0.33 mL, 2.4 mmol) followed by a solution of 2-amino-5-(3-bromophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one (0.82 g, 2 mmol) in dioxane and 1-hydroxy-2-propyne (0.47 mL, 0.006 mmol). The reaction mixture was heated to 35° C. for 30 min., poured into water and extracted with ethyl acetate. The extracts were combined, washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The resultant residue was purified by flash chromatography on silica gel, 1st in ethyl acetate 2nd 5% methanol/ethyl acetate as eluent to afford the title compound as a white solid, 0.39 g (48% yield), mp 90-93° C.; 1H NMR (DMSO-d6) δ 2.5 ((2H, under DMSO peak); 2.95 (s, 3 H); 3.5 (q, 2 H); 4.8 (t, 1 H); 6.6 (b, 2H); 7.1 (d, 2H); 7.15 (t, 2F); 7.2 (m, 2 H); 7.3 (m, 4 H); MS [(+)ESI] m/z=400.2 [M−H]+.

後処理

  1. stirringstirred for 5 min.
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by flash chromatography on silica gel, 1st in ethyl acetate 2nd 5% methanol/ethyl acetate as eluent

出典と根拠

ORDレコード
ord-e1700d82ac8d44c18148b7514ef11cb0
出典データセット
uspto-grants-2008_09
特許番号
US07423158B2

関連ノート

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