Sulfamic Acid → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

HRID 246553Notes

Reaction equation

HRID 246553 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([CH:21]=[O:22])=[CH:19][N:18]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.S(=O)(=O)([OH:33])N.Cl([O-])=O.[Na+].P([O-])(O)(O)=O.[K+]>O1CCOCC1.O.C(OCC)(=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([OH:33])=[O:22])=[CH:19][N:18]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 5987Sulfamic AcidHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 86677986HCID 86677986, compound

Product 1

HCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidYield 89.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred suspension of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (500 mg, 1.18 mmol) and sulfamic acid (685 mg, 7.05 mmol) in dioxane (25 mL) and water (0.556 mL) in an ice bath was added a solution of sodium chlorite (146 mg, 1.61 mmol) and potassium dihydrogen phosphate (1.92 g, 14.1 mmol) in water (2.78 mL). The reaction mixture was stirred at room temperature for overnight. The reaction mixture was diluted with ethyl acetate and water. The organic layer was separated, washed with brine then dried (sodium sulfate), filtered and concentrated in vacuo. The crude residue was recrystallized from ethyl acetate and hexane to give 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (467 mg, 89%) as a light yellow solid. This was used directly in the next step without further purification. LCMS, [M+H]=442.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialthen dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was recrystallized from ethyl acetate and hexane

Sources & evidence

ORD record
ord-3399a4cc9ff94030871ca10bad36f9c4
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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