Sodium hydride → 1-(2-amino-6-chloropyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid

HRID 1398621ノート

反応式

HRID 1398621 の反応式
[I: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:16][C:17]1[CH:22]=[C:21](Cl)[N:20]=[C:19]([NH2:24])[N:18]=1>CN(C=O)C>[NH2:24][C:19]1[N:20]=[C:21]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([I:1])[CH:10]=3)[C:6]([C:11]([OH:13])=[O:12])=[N:7]2)[CH:22]=[C:17]([Cl:16])[N:18]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 655222-Amino-4,6-dichloropyrimidineHCID 247287566-Iodo-1H-indazole-3-carboxylic acid

生成物 1

HCID 866696001-(2-amino-6-chloropyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 6-iodo-1H-indazole-3-carboxylic acid (3.00 g, 10.42 mmol) in dry DMF (50 mL) at 0° C. under an atmosphere of nitrogen was introduced sodium hydride (1.25 g of a 60% dispersion in mineral oil, 31.25 mmol). The reaction mixture was warmed to RT for 15 mins. 4,6-Dichloropyrimidin-2-amine (2.56 g, 15.62 mmol) was then added, and the solution warmed to 60° C. for 18 hr. After cooling to 0° C., the reaction was carefully quenched with water (50 mL) and acidified by addition of 0.5M aqueous citric acid. The resulting precipitate was collected by filtration, washed on the filter with 1:1 methanol/EtOAc and dried under vacuum to furnish the title compound as a beige solid: LC-MS: m/z=+415.85/417.90 (M+H)+. This compound, with LC-MS purity=70% UV, was used in the next step without further purification.

後処理

  1. temperaturethe solution warmed to 60° C. for 18 hr
  2. temperatureAfter cooling to 0° C.
  3. customthe reaction was carefully quenched with water (50 mL)
  4. additionacidified by addition of 0.5M aqueous citric acid
  5. filtrationThe resulting precipitate was collected by filtration
  6. washwashed on the
  7. filtrationfilter with 1:1 methanol/EtOAc
  8. customdried under vacuum

出典と根拠

ORDレコード
ord-2d89aab53fac448c93e5dfd5aee10e6b
出典データセット
uspto-grants-2014_12
特許番号
US08901313B2

反応ノート

読み込み中…