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

HRID 246075Notes

Reaction equation

HRID 246075 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:15]3[N:16]=[C:17]4[C:23]([CH:24]=[O:25])=[CH:22][N:21]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:18]4=[N:19][CH:20]=3)=[N:7][N:8]2[CH:11]2[CH2:14][O:13][CH2:12]2)=[CH:4][CH:3]=1.S(=O)(=O)([OH:36])N.Cl([O-])=O.[Na+].P([O-])(O)(O)=O.[K+]>O1CCOCC1.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:15]3[N:16]=[C:17]4[C:23]([C:24]([OH:36])=[O:25])=[CH:22][N:21]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[C:18]4=[N:19][CH:20]=3)=[N:7][N:8]2[CH:11]2[CH2:12][O:13][CH2:14]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 5987Sulfamic AcidHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 866779432-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 712801872-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidYield 111.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (293 mg, 0.63 mmol) in 1,4-dioxane (20 ml) and water (4 ml) at 0° C. was added sulfamic acid (365 mg, 3.76 mmol). Then a solution of sodium chlorite (80%, 92 mg, 0.82 mmol) and potassium dihydrogen phosphate (1.02 g, 7.52 mmol) in water (16 ml) was added over ˜15 min. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 30 min. THF (20 ml) was added and stirred was continued for 2 h. The reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organic layers were washed with brine then dried over MgSO4 and concentrated to afford 340 mg of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as an off-white powder.

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. additionTHF (20 ml) was added
  4. stirringstirred
  5. waitwas continued for 2 h
  6. additionThe reaction mixture was diluted with water
  7. extractionextracted with EtOAc (3×)
  8. washThe combined organic layers were washed with brine
  9. dry with materialthen dried over MgSO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-246539ae1a8f42f58cd63e8b78cb02f6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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