Citric Acid → 1-(2-Aminopyrimidin-4-yl)-6-bromoindazole-3-carboxylic acid

HRID 1398576노트

반응식

HRID 1398576 반응식
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[N:18]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[NH2:23][C:19]1[N:20]=[C:21]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=3)[C:6]([C:11]([OH:13])=[O:12])=[N:7]2)[CH:22]=[CH:17][N:18]=1

참가 물질

6

반응물 4

HCID 311Citric AcidHCID 24758Sodium hydride2회HCID 2233322-Amino-4-chloropyrimidineHCID 247280286-Bromo-1H-indazole-3-carboxylic acid

생성물 1

HCID 681819661-(2-Aminopyrimidin-4-yl)-6-bromoindazole-3-carboxylic acid수율 83.6%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To suspension of 6-bromo-1H-indazole-3-carboxylic acid (5 g, 20.77 mmol) in DMF (40 mL) was added NaH (60%, 1.7 g, 41.5 mmol). The mixture was stirred at RT for 10 min, followed by addition of 4-chloro-pyrimidin-2-ylamine (4.0 g, 31 mmol). The mixture was heated at 65° C. for 2 hr. The reaction cooled to RT, then another 1 eq NaH added (ca 0.78 g). Heating continued at 65° C. overnight. Reaction mixture was allowed to cool to RT. The mixture was quenched by portionwise addition to water (10 mL) resulting in formation of a precipitate. The mixture was acidified with 0.5M aq citric acid. The precipitate was collected by suction filtration through a fritted sinter funnel and washed with MeOH/EtOAc (1/1) and was thoroughly dried under high vacuum to give the title compound as a beige solid (5.8 g, LC-MS purity=88%); LC-MS: m/z=+333.85/335.80 (M+H)+.

후처리

  1. temperatureThe mixture was heated at 65° C. for 2 hr
  2. temperatureThe reaction cooled to RT
  3. temperatureHeating
  4. waitcontinued at 65° C. overnight
  5. customReaction mixture
  6. temperatureto cool to RT
  7. customThe mixture was quenched by portionwise addition to water (10 mL)
  8. customresulting in formation of a precipitate
  9. filtrationThe precipitate was collected by suction filtration through a fritted sinter funnel
  10. washwashed with MeOH/EtOAc (1/1)
  11. customwas thoroughly dried under high vacuum

출처 및 근거

ORD 기록
ord-d28320273b6c46e99fb8a1a880792e0e
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901313B2

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