4-Methylmorpholine → (2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentyloxyimino-N-pyrazin-2-ylacetamide

HRID 600949ノート

反応式

HRID 600949 の反応式
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)/[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[N:23]1[CH:28]=[CH:27][N:26]=[CH:25][C:24]=1[NH2:29].CN1CCOCC1.C(OCC)(=O)C>CN(C)C=O.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)/[C:13]([NH:29][C:24]2[CH:25]=[N:26][CH:27]=[CH:28][N:23]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

参加物

7

反応物 4

HCID 79724-Methylmorpholine2 回HCID 8857Ethyl AcetateHCID 78747Aminopyrazine2 回HCID 87416741HCID 87416741、化合物

生成物 1

HCID 59745099(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentyloxyimino-N-pyrazin-2-ylacetamide収率 52.4%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
0 °C

実験手順

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (prepared as in Example 1, 97 mg, 0.28 mmol), pyrazin-2-ylamine (29 mg, 0.31 mmol) and 4-methylmorpholine (123 μL, 1.12 mmol) were combined in N,N-dimethylformamide (1.5 mL) and cooled to 0° C. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (117 mg, 0.31 mmol) was added and the ice bath was removed. After stirring 16 h, further portions of pyrazin-2-ylamine (10 mg, 0.11 mmol), 4-methylmorpholine (41 μL, 0.37 mmol) and O-(7-azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (39 mg, 0.10 mmol) were added. After stirring an additional 3 h, the reaction mixture was treated with ethyl acetate (100 mL) and saturated aqueous brine solution (200 mL). The phases were separated and the organic phase was washed with a 0.2 M aqueous potassium bisulfate solution and saturated aqueous brine solution (50 mL) and a 1:1 mixture of saturated aqueous sodium bicarbonate solution and saturated aqueous brine solution (50 mL) then dried over magnesium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-N-pyrazin-2-yl-acetamide (62 mg, 52%) as a clear, colorless film which was then lyophilized from aqueous acetonitrile to afford a white solid: LC-MS (ESI) m/e calcd for C18H19ClN4O4S [M+] 422.08, found 423 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.68 (m, 4 H, 2×CH2), 1.91 (m, 4 H, 2×CH2), 3.32 (s, 3 H, SO2CH3), 4.98 (m, 1 H, OCH), 7.57 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.68 (d, Jm=1.5 Hz, 1 H, Ar), 8.22 (d, Jo=8.2 Hz, 1 H, Ar), 8.33 (m, 1 H, Ar), 8.41 (m, 1 H, Ar), 9.29 (brs, 1 H, Ar), 9.56 (s, 1 H, NH).

後処理

  1. customthe ice bath was removed
  2. stirringAfter stirring an additional 3 h
  3. customThe phases were separated
  4. washthe organic phase was washed with a 0.2 M aqueous potassium bisulfate solution and saturated aqueous brine solution (50 mL)
  5. additiona 1:1 mixture of saturated aqueous sodium bicarbonate solution and saturated aqueous brine solution (50 mL)
  6. dry with materialthen dried over magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-4d9be61688a74dadb529d309bd625897
出典データセット
uspto-grants-2011_03
特許番号
US07902248B2

反応ノート

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