Water → 2-(3-Chloro-propyl)-3-oxo-2,3-dihydro-indazole-1-carboxylic acid ethyl ester

HRID 2389478ノート

反応式

HRID 2389478 の反応式
[CH2:1]([O:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8](=[O:15])[NH:7]1)=[O:5])[CH3:2].[H-].[Na+].I[CH:19]([Cl:22])[CH2:20][CH3:21].O>CN(C=O)C>[CH2:1]([O:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8](=[O:15])[N:7]1[CH2:21][CH2:20][CH2:19][Cl:22])=[O:5])[CH3:2]

参加物

6

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 584113Ethyl 3-oxo-2,3-dihydro-1H-indazole-1-carboxylateHCID 23271035Chloroiodopropane

生成物 1

HCID 693147462-(3-Chloro-propyl)-3-oxo-2,3-dihydro-indazole-1-carboxylic acid ethyl ester収率 13.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒3 回

実験手順

To a solution of 3-oxo-2,3-dihydro-indazole-1-carboxylic acid ethyl ester (410 mg, 2 mmol) dissolved in dry DMF (10 ml) is added sodium hydride (60% w/w in oil, 120 mg, 3 mmol). The resulting cloudy solution is allowed to stir for 1 h at rt and is added dropwise under inert atmosphere via a syringe onto a solution of iodochloropropane (268 μl, 2.5 mmol) in dry DMF (2 ml). The resulting solution is allowed to stir at rt overnight. By addition of water and evaporation under reduced pressure most of the DMF is removed from the crude mixture. The residue is dissolved in AcOEt (25 ml) and the resulting organic phase is washed 3 times with water and once with brine. The crude product is purified by chromatography on silica gel (AcOEt/heptane, 2:3), yielding the title compound (78 mg) in 15% as a colourless oil: tR=2.17 min (LC-2), ESI-MS (pos.): m/z 283.05 [M+H]+; 1H-NMR (CDCl3): δ (ppm) 1.38 (t, 3H, CH3), 2.08 (quint., 2H, CH2CH2N), 3.42 (t, 2H, CH2Cl), 4.25 (t, 2H, NCH2), 4.39 (q, 2H, OCH2CH3), 7.22 (t, 1Harom), 7.53 (t, 1Harom), 7.79 (t, 2Harom), and 3-(3-chloro-propoxy)-indazole-1-carboxylic acid ethyl ester (125 mg) in 24% as a colourless oil: tR=2.49 min (LC-2), ESI-MS (pos.): m/z 283.05 [M+H]+; 1H-NMR (CDCl3): δ (ppm) 1.44 (t, 3H, CH3), 2.26 (quint., 2H, CH2CH2N), 3.71 (t, 2H, CH2Cl), 4.49 (q, 2H, OCH2CH3), 4.59 (t, 2H, OCH2CH2), 7.20 (t, 1H, m), 7.46 (t, 1Harom), 7.59 (d, 1 Harom), 8.02 (d, 1Harom). 3-(3-Chloro-propoxy)-indazole-1-carboxylic acid ethyl ester is used as alkylating agent D-06d in the preparation of Precursor D-06b.

後処理

  1. stirringto stir at rt overnight
  2. customis removed from the crude mixture
  3. dissolutionThe residue is dissolved in AcOEt (25 ml)
  4. washthe resulting organic phase is washed 3 times with water
  5. customThe crude product is purified by chromatography on silica gel (AcOEt/heptane, 2:3)

出典と根拠

ORDレコード
ord-17ed8947d48e4bdfa8d5e69c36154ec2
出典データセット
uspto-grants-2012_09
特許番号
US08273740B2

反応ノート

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