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 246081노트

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HRID 246081 반응식
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]

참가 물질

6

반응물 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

생성물 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 isopropylamide수율 68%

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 887Methanol용매2회HCID 8028Tetrahydrofuran용매

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온도
50 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-ed4278fdb0aa47b4a866850c072dc767
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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