Sulfolane → Methyl 6-bromo-1-isopropyl-3-methyl-1H-indazole-4-carboxylate

HRID 85481ノート

反応式

HRID 85481 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:5]2[C:6]([CH:14]=O)=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.S1(CCCC1)(=O)=O.C([BH3-])#N.[Na+]>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:5]2[C:6]([CH3:14])=[N:7][N:8]([CH:11]([CH3:12])[CH3:13])[C:9]=2[CH:10]=1

参加物

7

反応物 4

HCID 31347SulfolaneHCID 521998p-Toluenesulfonic acid monohydrateHCID 5003444Sodium cyanoborohydrideHCID 71742648Methyl 6-bromo-3-formyl-1-isopropyl-1H-indazole-4-carboxylate

生成物 1

HCID 67466747Methyl 6-bromo-1-isopropyl-3-methyl-1H-indazole-4-carboxylate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

To a stirred solution of methyl 6-bromo-3-formyl-1-isopropyl-1H-indazole-4-carboxylate (4.5 g, 13.84 mmol) in DMF (31.5 mL) was added p-toluenesulfonic acid monohydrate (0.342 g, 1.8 mmol), p-toluenesulfonyl hydrazide (3.35 g, 18.0 mmol) followed by sulfolane (31.5 mL), and the reaction mixture was stirred at 100° C. for 1 h. The reaction mixture was cooled to room temperature and sodium cyanoborohydride (3.489 g, 55.0 mmol) was added portion wise over a period of 25 min. The resulting reaction mixture was stirred at 100° C. for 2 h and then at RT for 6 h. The reaction mixture was diluted with water and extracted with ethyl acetate (4×300 mL). The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude residue (4.4 g) was purified by silica gel chromatography (eluent: 0-5% ethyl acetate: pet ether) to afford the title compound as an off white solid (2.95 g, 68%). 1H NMR (CDCl3, 400 MHz): δ 1.559 (d, J=6.8 Hz, 6H), 2.674 (s, 3H), 3.976 (s, 3H), 4.667-4.767 (m, 1H), 7.715 (d, J=1.6 Hz, 1H), 7.761 (d, J=1.6 Hz, 1H).-LCMS (ES+): 98.63%, 313.06 [M+H] ion present.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe resulting reaction mixture
  3. stirringwas stirred at 100° C. for 2 h
  4. waitat RT for 6 h
  5. extractionextracted with ethyl acetate (4×300 mL)
  6. washThe combined organic layers were washed with water, brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue (4.4 g) was purified by silica gel chromatography (eluent: 0-5% ethyl acetate: pet ether)

出典と根拠

ORDレコード
ord-379085084d0b4edab057520715868510
出典データセット
uspto-grants-2014_09
特許番号
US08846935B2

反応ノート

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