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

HRID 2389478노트

반응식

HRID 2389478 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매3회

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-17ed8947d48e4bdfa8d5e69c36154ec2
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08273740B2

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