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Diisopropylethylamine → 5-((5-((6-Bromobenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)methyl)-5-methylimidazolidine-2,4-dione

HRID 2281175
ノート
印刷プレビュー

反応式

HRID 2281175 の反応式
[Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([CH2:9][C:10]([NH:12][NH2:13])=[O:11])[S:8][C:4]=2[CH:3]=1.[CH3:16][C:17]1([CH2:24][C:25](O)=O)[C:21](=[O:22])[NH:20][C:19](=[O:23])[NH:18]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>O1CCOCC1.C(Cl)Cl>[Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([CH2:9][C:10]3[O:11][C:25]([CH2:24][C:17]4([CH3:16])[NH:18][C:19](=[O:23])[NH:20][C:21]4=[O:22])=[N:13][N:12]=3)[S:8][C:4]=2[CH:3]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 81531Diisopropylethylamine2 回HCID 111923Propylphosphonic anhydride2 回HCID 2903362-(4-Methyl-2,5-dioxoimidazolidin-4-yl)acetic acidHCID 899219952-(6-Bromobenzo[d]thiazol-2-yl)acetohydrazide

生成物 1

HCID 899223305-((5-((6-Bromobenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)methyl)-5-methylimidazolidine-2,4-dione収率 55%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

To a solution of 2-(6-bromobenzo[d]thiazol-2-yl)acetohydrazide (1.0 g, 3.5 mmol) (prepared as described in WO 2011/074560) in dioxane (10 mL) was added 2-(4-methyl-2,5-dioxoimidazolidin-4-yl)acetic acid (0.80 g, 4.2 mmol), T3P (50% in EtOAc, 5.20 mL, 8.74 mmol) and DIPEA (3.1 mL, 17.5 mmol). The reaction mixture was stirred at 90° C. for 6 h. Additional DIPEA (3.1 mL, 18 mmol) and T3P (50% in EtOAc, 3.1 mL, 1.8 mmol) were added. The reaction mixture was heated at 95° C. for 12 h. The reaction mixture was diluted with DCM, and the organic portion washed with 1.5 M K3PO4, 1.0 M HCl solution and brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by ISCO silica gel chromatography eluting with 0-15% MeOH/DCM over 30 min gradient to give racemic material (811 mg, 1.92 mmol, 55.0% yield) as a yellow solid. The enantiomers were separated by preparative chiral SFC (Kromasil 5-Cellucoat 21×250 mm ID, 5 μm, 65 mL/min, 150 bar, 35° C., 25% MeOH/77% CO2) to afford isomer A as Example 23A (Rt=7.8 min, 37% yield), LCMS (method B) Rt=1.6 min, m/z=423.9 (M+H)+; and isomer B as Example 23B (Rt=11.2 min, 35% yield), LCMS (method B) retention time=1.6 min, m/z=423.9 (M+H)+. For Example 23B: 1H NMR (400 MHz, CDCl3) δ 8.26 (br. s., 1H), 8.01 (d, J=1.8 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 7.60 (dd, J=8.8, 2.0 Hz, 1H), 6.54 (s, 1H), 4.71 (d, J=2.0 Hz, 2H), 3.40-3.21 (m, 2H), 1.59 (s, 3H).

後処理

  1. temperatureThe reaction mixture was heated at 95° C. for 12 h
  2. washthe organic portion washed with 1.5 M K3PO4, 1.0 M HCl solution and brine
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by ISCO silica gel chromatography
  7. washeluting with 0-15% MeOH/DCM over 30 min gradient

出典と根拠

ORDレコード
ord-01fe492b3d4f47cdabbd20ec63c7b30b
出典データセット
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09139578B2

反応ノート

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