4-Methyloxybenzyl chloride → 1-(4-Methoxybenzyl)-1H-indazole-6-carbaldehyde

HRID 1410336ノート

反応式

HRID 1410336 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:10]=[O:11])[CH:8]=2)[CH:3]=[N:2]1.CC([O-])(C)C.[K+].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26]Cl)=[CH:22][CH:21]=1>CN(C=O)C>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([CH:10]=[O:11])[CH:8]=3)[CH:3]=[N:2]2)=[CH:22][CH:21]=1

参加物

5

反応物 3

HCID 699934-Methyloxybenzyl chloride2 回HCID 185383681H-Indazole-6-carbaldehydeHCID 23665647Potassium tert-butoxide

生成物 1

HCID 866815121-(4-Methoxybenzyl)-1H-indazole-6-carbaldehyde収率 72%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 1H-indazole-6-carbaldehyde (1.5 g, 10.3 mmol) in DMF (10 mL) at 0° C. was added KOtBu (1.4 g, 12.4 mmol) and let stir for 10 min. PMBCl (1.7 mL, 12.4 mmol) was then added and let slowly warm to room temperature. After 1.5 h the reaction was quenched with NH4Cl. The product was extracted with Et2O and the organic layers was washed brine and then dried over MgSO4. The solvent was removed and the crude material (mixture of N1 and N2 isomers) was dried under high vacuum. To the resulting residue was added PMBCl (0.70 mL, 5.15 mmol) and the mixture heated to 170° C. for 2.5 h. Cooled to room temperature and purified residue using Biotage Isolera (silica gel, 20-50% EtOAc in hexane) which gave the title compound (1.97 g, 72%). 1H NMR (400 MHz, CDCl3) δ 10.09 (s, 1H), 8.12 (s, 1H), 7.91 (s, 1H), 7.85 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.21 (d, J=8.5 Hz, 2H), 6.85 (d, J=8.6 Hz, 2H), 5.62 (s, 2H), 3.77 (s, 3H); MS ESI 266.9 [M+H]+, calcd for [C16H14N2O2+H]+ 267.1.

後処理

  1. customAfter 1.5 h the reaction was quenched with NH4Cl
  2. extractionThe product was extracted with Et2O
  3. washthe organic layers was washed brine
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed
  6. customthe crude material (mixture of N1 and N2 isomers) was dried under high vacuum
  7. temperaturethe mixture heated to 170° C. for 2.5 h
  8. temperatureCooled to room temperature
  9. custompurified residue

出典と根拠

ORDレコード
ord-82e4ac875b3b4dcb90f880731c57ad92
出典データセット
uspto-grants-2014_12
特許番号
US08921545B2

反応ノート

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