2-(1-allyl-6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide → 2-(6-chloro-1-propyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 246042Notes

Reaction equation

HRID 246042 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:43])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH2:32][CH:33]=[CH2:34])[N:23]=4)[N:20]=3)[N:15]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]>CO.[Pd]>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:43])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH2:32][CH2:33][CH3:34])[N:23]=4)[N:20]=3)[N:15]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:41])([CH3:40])[CH3:42])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

Participants

4

Reactant 1

HCID 866779372-(1-allyl-6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Product 1

HCID 712861762-(6-chloro-1-propyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amideYield 76.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 2-(1-allyl-6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (50 mg, 0.08 mmol) in MeOH (6 ml) was added 10% Pd on carbon (wet, 17 mg). The reaction mixture was stirred under an atmosphere of hydrogen (balloon) for 1.5 h then filtered over Celite, rinsing with EtOAc. The filtrate was concentrated and the residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane to afford 38 mg (76%) of 2-(6-chloro-1-propyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a viscous colorless oil.

Workup

  1. filtrationthen filtered over Celite
  2. washrinsing with EtOAc
  3. concentrationThe filtrate was concentrated
  4. customthe residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane

Sources & evidence

ORD record
ord-8664be2ce32d402da7fd123802fa20f8
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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