Ammonium formate → 2-(1-azetidin-3-yl-6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 246081ノート

反応式

HRID 246081 の反応式
C([O-])=O.[NH4+].[CH:5]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH:30]4[CH2:33][N:32](C(C5C=CC=CC=5)C5C=CC=CC=5)[CH2:31]4)[N:21]=3)[N:18]=2)[N:13]([CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])[CH:12]=1)=[O:10])([CH3:7])[CH3:6]>CO.C1COCC1.[Pd]>[CH:5]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH:30]4[CH2:33][NH:32][CH2:31]4)[N:21]=3)[N:18]=2)[N:13]([CH2:47][O:48][CH2:49][CH2:50][Si:51]([CH3:53])([CH3:52])[CH3:54])[CH:12]=1)=[O:10])([CH3:7])[CH3:6]

参加物

6

反応物 2

HCID 2723923Ammonium formateHCID 712793702-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

生成物 1

HCID 712795152-(1-azetidin-3-yl-6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide収率 68%

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 887Methanol溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
50 °C

実験手順

In a round-bottomed flask ammonium formate (135 mg, 2.15 mmol) was dissolved in MeOH (1.5 mL). This solution was added to a solution of 2-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide (74 mg, 0.107 mmol) in THF (1.5 mL) which caused a white precipitate to form. This slurry was transferred via pipet to a pressure tube containing 10% palladium on carbon (wet, 23 mg) in MeOH (1 mL). The tube was sealed and heated at 50° C. for 4 h then cooled to room temperature overnight. The mixture was filtered over Celite, rinsing with CH2Cl2. The filtrate was concentrated and the residue was absorbed onto SiO2 and chromatographed with 0% to 10% MeOH/CH2Cl2 (0.5% NH4OH) to afford 38 mg (68%) of 2-(1-azetidin-3-yl-6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a pale yellow foamy solid.

後処理

  1. customto form
  2. customThis slurry was transferred via pipet to a pressure tube
  3. customThe tube was sealed
  4. temperaturethen cooled to room temperature overnight
  5. filtrationThe mixture was filtered over Celite
  6. washrinsing with CH2Cl2
  7. concentrationThe filtrate was concentrated
  8. customthe residue was absorbed onto SiO2
  9. customchromatographed with 0% to 10% MeOH/CH2Cl2 (0.5% NH4OH)

出典と根拠

ORDレコード
ord-ed4278fdb0aa47b4a866850c072dc767
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…