Hydrazine → 6-fluoro-3-methyl-1H-indazole

HRID 343140

반응식

HRID 343140 반응식
[CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1F)=O.[NH2:12][NH2:13]>CCO>[F:10][C:7]1[CH:6]=[C:5]2[C:4]([C:2]([CH3:1])=[N:12][NH:13]2)=[CH:9][CH:8]=1

참가 물질

4

반응물 2

HCID 9321HydrazineHCID 677702,4-Difluoroacetophenone

생성물 1

HCID 1784343226-fluoro-3-methyl-1H-indazole수율 68.5%

시약·촉매·용매 1

HCID 702Ethanol용매2회

실험 절차

In a sealed flask were combined 12.99 g (83.2 mmol) 2,4-Difluoroacetophenone, 8.80 g (274 mmol, 3.3 equiv) Hydrazine and 8.7 mL EtOH and heated at 150° C. for 18 h. The resultant solid is dissolved in 150 mL EtOH, precipitated with 500 mL H2O, cooled, filtered, air and pump dried to give 8.56 g (57.0 mmol) 6-Fluoro-3-methyl-1H-indazole which is used without characterization. The material thus obtained is combined with 6.35 g (62.7 mmol, 1.1 equiv) Et3N and 1.39 g (11.4 mmol, 0.2 equiv) DMAP in 110 mL CH3CN cooled to 0° C. 14.93 g (68.4 mmol, 1.2 equiv) (BOC)2O in 80 mL CH3CN is added dropwise with stirring at 0° C. and the resultant reaction mixture stirred 2 h at 0° C. followed by 18 h at ambient temperature. The solvent is removed in vacuo and the crude material partitioned between EtOAc (200 mL) and H2O (100 mL). The pH is adjusted to 2.0 with 1N HCl, the organic phase separated, dried (MgSO4), filtered and concentrated in vacuo to an orange solid which is purified by filtration through a pad of 60 g silica gel eluted with 1.2 L DCM. The filtrate is concentrated in vacuo to give 12.68 g (50.7 mmol) of 6-Fluoro-3-methyl-indazole-1-carboxylic acid tert-butyl ester as a tan crystalline solid: 1H NMR (CDCl3, 300 MHz) δ7.78 (d, 1H, J=9.8), 7.57 (m, 1H), 7.07 (m, 1H), 2.57 (s, 3H), 1.72 (s, 9H); TLC Rf =0.52 (DCM).

후처리

  1. customIn a sealed flask were combined
  2. customprecipitated with 500 mL H2O
  3. temperaturecooled
  4. filtrationfiltered
  5. customair and pump dried

출처 및 근거

ORD 기록
ord-9067b273075a45a9943f7d10cd6197c5
출처 데이터셋
uspto-grants-1999_01
특허 번호
US05859007

연결된 노트

불러오는 중…