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

반응식

HRID 30575 반응식
[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

참가 물질

9

반응물 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

생성물 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-one수율 48%

시약·촉매·용매 4

HCID 83717Copper iodide촉매HCID 498840Bis(benzonitrile)palladium chloride촉매HCID 962Water용매HCID 312751,4-Dioxane용매2회

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온도
35 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-e1700d82ac8d44c18148b7514ef11cb0
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423158B2

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