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 246081Notes

Reaction equation

HRID 246081 reaction equation
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]

Participants

6

Reactant 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

Product 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 isopropylamideYield 68%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-ed4278fdb0aa47b4a866850c072dc767
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…