N-Iodosuccinimide → 5-iodo-6-methoxy-N-methyl-2-pyridinamine

HRID 1280460

反応式

HRID 1280460 の反応式
[CH3:1][O:2][C:3]1[N:8]=[C:7]([NH:9][CH3:10])[CH:6]=[CH:5][CH:4]=1.C1C(=O)N([I:18])C(=O)C1>CN(C=O)C>[I:18][C:4]1[CH:5]=[CH:6][C:7]([NH:9][CH3:10])=[N:8][C:3]=1[O:2][CH3:1]

参加物

4

反応物 2

HCID 120273N-IodosuccinimideHCID 70191686-methoxy-N-methylpyridin-2-amine

生成物 1

HCID 234358665-iodo-6-methoxy-N-methyl-2-pyridinamine収率 97.7%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

6-Methoxy-N-methyl-2-pyridinamine (17.24 g, 124 mmol) is dissolved in DMF (160 mL) and cooled to 0° C. followed by the addition of NIS (28 g, 124 mmol, 1 equiv), at a rate which keeps the reaction temperature below 10° C. The reaction is then allowed to warm to room temperature and stirred for 1 h. The reaction is distilled to dryness in vacuo and the residue is dissolved in CH2Cl2 and passed through a silica plug eluting with heptane/EtOAc (9/1) affording 32 g of crude 5-iodo-6-methoxy-N-methyl-2-pyridinamine. The crude 5-iodo-6-methoxy-N-methyl-2-pyridinamine is dissolved in diethyl ethoxymethylenemalonate (32 mL) and the mixture is heated at 140° C. for 2 h, then cooled to room temperature and passed through a silica plug eluting with heptane/EtOAc (19/1, 0/1). The product is then dissolved in Eaton's reagent (132 mL) and heated at 100° C. for 40 min, cooled to rt and poured into Na2CO3. The basic aqueous layer is then extracted with CH2Cl2 (3×), washed with water, and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography (heptane/EtOAc, 4/1, 1/1, CH2Cl2/MeOH 19/1) the desired product is then triturated with MeOH to afford 7.9 g (16%) of ethyl 6-iodo-7-methoxy-1-methyl-4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylate. Physical characteristics are as follows: 1H NMR (CDCl3) δ 9.04, 8.52, 4.41, 4.13, 3.91, 1.43; IR (diffuse reflectance) 2491, 2427, 2350, 2282, 2242, 1678, 1632, 1613, 1579, 1384, 1309, 1275, 1227, 1106, 804, cm−1; MS (EI) m/z 388, 344, 343, 317, 316, 185, 159, 86, 84, 51; Anal calcd for C13H13IN2O4: C, 40.23; H, 3.38; N, 7.22. Found: C, 40.20; H, 3.40; N, 7.16.

後処理

  1. customthe reaction temperature below 10° C
  2. temperatureto warm to room temperature
  3. distillationThe reaction is distilled to dryness in vacuo
  4. dissolutionthe residue is dissolved in CH2Cl2
  5. washeluting with heptane/EtOAc (9/1)

出典と根拠

ORDレコード
ord-64c64fa4c42746d6ad1fa1a5bfb47d1e
出典データセット
uspto-grants-2002_09
特許番号
US06451811B2

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