Lithium Hexamethyldisilazide → 7-fluoro-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 706539ノート

反応式

HRID 706539 の反応式
[CH:1]([C:4]1[N:9]=[C:8]([CH2:10][N:11]2[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([NH2:20])[C:14]=3[C:13]([CH3:21])=[N:12]2)[CH:7]=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[F:22][C:23]1[CH:28]=[CH:27][N:26]2[C:29]([C:32](OCC)=[O:33])=[CH:30][N:31]=[C:25]2[CH:24]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:22][C:23]1[CH:28]=[CH:27][N:26]2[C:29]([C:32]([NH:20][C:15]3[CH:16]=[CH:17][CH:18]=[C:19]4[C:14]=3[C:13]([CH3:21])=[N:12][N:11]4[CH2:10][C:8]3[CH:7]=[CH:6][CH:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[N:9]=3)=[O:33])=[CH:30][N:31]=[C:25]2[CH:24]=1

参加物

5

反応物 3

HCID 2733832Lithium HexamethyldisilazideHCID 67259301Ethyl 7-fluoroimidazo[1,2-a]pyridine-3-carboxylateHCID 679746421-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-amine

生成物 1

HCID 679760637-fluoro-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide収率 73%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

1-((6-Isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-amine (Preparation D; 0.673 g, 2.40 mmol) and ethyl 7-fluoroimidazo[1,2-a]pyridine-3-carboxylate (Step C, 0.500 g, 2.40 mmol) were dissolved in dry THF (24 mL) and chilled to 0° C. LiHMDS (5.28 mL, 5.28 mmol, 1M in THF) was added by syringe over a five-minute period. Once the addition was complete, the reaction mixture was removed from the cooling bath and allowed to warm to ambient temperature. The mixture was quenched with saturated ammonium chloride solution and extracted with EtOAc. The combined organic extracts were washed with saturated sodium bicarbonate solution, dried over sodium sulfate and concentrated. The crude material was purified by column chromatography (100% ethyl acetate) to afford 775 mg (73%) of 7-fluoro-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide.

後処理

  1. additionOnce the addition
  2. customthe reaction mixture was removed from the cooling bath
  3. temperatureto warm to ambient temperature
  4. customThe mixture was quenched with saturated ammonium chloride solution
  5. extractionextracted with EtOAc
  6. washThe combined organic extracts were washed with saturated sodium bicarbonate solution
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography (100% ethyl acetate)

出典と根拠

ORDレコード
ord-92f5f877acd3440590d8e65c117afe32
出典データセット
uspto-grants-2015_11
特許番号
US09174981B2

反応ノート

読み込み中…