Potassium Carbonate → HCID 71288191, compound

HRID 245930Notes

Reaction equation

HRID 245930 reaction equation
[OH:1][CH2:2][CH2:3][NH:4][C:5]([C@H:7]([NH:9][C:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]3[C:29]4[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=4)[N:23]([CH3:31])[N:22]=3)[N:19]=2)[N:14]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[CH:13]=1)=[O:11])[CH3:8])=O.CCN(S(F)(F)F)CC.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[O:1]1[CH2:2][CH2:3][N:4]=[C:5]1[C@H:7]([NH:9][C:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:21]3[C:29]4[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=4)[N:23]([CH3:31])[N:22]=3)[N:19]=2)[N:14]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:38])([CH3:37])[CH3:39])[CH:13]=1)=[O:11])[CH3:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 123472(Diethylamino)sulfur trifluorideHCID 712881872-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-amide

Product 1

HCID 71288191HCID 71288191, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-76 °C

Procedure

In a round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-amide (126 mg, 0.23 mmol) was dissolved in dichloromethane (2.2 ml). The solution was cooled to −76° C. and DAST (45 μl, 0.34 mmol) was added. The pale yellow reaction mixture was stirred at −76° C. for 6 h then anhydrous potassium carbonate (64 mg, 0.46 mmol) was added in one portion. The reaction mixture was allowed to warm to room temperature, quenched with saturated aqueous NaHCO3 and extracted with dichloromethane (3×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-90% EtOAc) to afford 86 mg (71%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4,5-dihydro-oxazol-2-yl)-ethyl]-amide as a light yellow solid.

Workup

  1. temperatureto warm to room temperature
  2. customquenched with saturated aqueous NaHCO3
  3. extractionextracted with dichloromethane (3×)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-90% EtOAc)

Sources & evidence

ORD record
ord-e0b71cac531f4477a2e5559cd5c85da0
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…