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Methyl iodide → 2-(4-tert-butylphenyl)-N-[(E)-isoquinolin-5-ylmethylideneamino]-N-methylcyclopropane-1-carboxamide

HRID 446770
ノート
印刷プレビュー

反応式

HRID 446770 の反応式
[H-].[Na+].[C:3]([C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:15][CH:14]2[C:16]([NH:18]/[N:19]=[CH:20]/[C:21]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:22]=2[CH:23]=[CH:24][N:25]=[CH:26]3)=[O:17])=[CH:9][CH:8]=1)([CH3:6])([CH3:5])[CH3:4].[CH3:31]I>CN(C=O)C>[C:3]([C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:15][CH:14]2[C:16]([N:18]([CH3:31])/[N:19]=[CH:20]/[C:21]2[CH:30]=[CH:29][CH:28]=[C:27]3[C:22]=2[CH:23]=[CH:24][N:25]=[CH:26]3)=[O:17])=[CH:9][CH:8]=1)([CH3:6])([CH3:4])[CH3:5]
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

5

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 445554402-(4-tert-butylphenyl)-N-[(E)-isoquinolin-5-ylmethylideneamino]cyclopropane-1-carboxamide

生成物 1

HCID 461859942-(4-tert-butylphenyl)-N-[(E)-isoquinolin-5-ylmethylideneamino]-N-methylcyclopropane-1-carboxamide収率 50%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide
溶媒

反応条件

温度
0 °C

実験手順

To a 0° C. suspension of NaH (16 mg, 0.6 mmol) in DMF (1 mL), (E)-2-(4-tert-butylphenyl)-N′-(isoquinolin-5-ylmethylene)cyclopropanecarbohydrazide (200 mg, 0.53 mmol) was added portionwise under nitrogen atmosphere. After being stirred for 1 h at 0° C., MeI (0.15 g, 1.0 mmol) was added and the reaction mixture stirred at RT for 1 h. The reaction mixture was then quenched with ice water and stirred for an additional 10 minutes. The precipitated solid was filtered and dried in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography using 20% ethyl acetate in hexanes to afford (E)-2-(4-tert-butylphenyl)-N′-(isoquinolin-5-ylmethylene)-N-methylcyclopropanecarbohydrazide (30 mg, 50%) as an off-white solid. 1H NMR (500 MHz, CDCl3): δ 9.24 (bs, 1 H), 8.50-8.41 (m, 1 H), 8.26-8.20 (m, 1 H), 8.02-7.94 (m, 2 H), 7.66-7.58 (m, 2 H), 7.39 (d, J=7.2 Hz, 2 H), 7.14 (d, J=7.2 Hz, 2 H), 3.28 (s, 3 H), 3.39-3.12 (m, 1 H), 2.63-2.56 (m, 1 H), 1.84-1.78 (m, 1 H), 1.49-1.38 (m, 1 H), 1.37 (s, 9 H). MS: M+H: m/z=386.2 and HPLC: 91%, (Condition-G).

後処理

  1. additionwas added portionwise under nitrogen atmosphere
  2. stirringthe reaction mixture stirred at RT for 1 h
  3. customThe reaction mixture was then quenched with ice water
  4. stirringstirred for an additional 10 minutes
  5. filtrationThe precipitated solid was filtered
  6. customdried in vacuo
  7. customto obtain the crude product
  8. customThe crude material was purified via silica gel column chromatography

出典と根拠

ORDレコード
ord-e11d2896179c490c9406318bd0c42ef8
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08481532B2

反応ノート

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