Sulfamic Acid → 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

HRID 246100Notes

Reaction equation

HRID 246100 reaction equation
[Cl: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])=[C:4]([F:31])[CH:3]=1.S(=O)(=O)([OH:34])N.Cl([O-])=O.[Na+].OP([O-])(O)=O.[K+]>C1COCC1.O.C(OCC)(=O)C>[Cl: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:34])=[O:22])=[CH:19][N:18]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:28])([CH3:30])[CH3:29])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[C:4]([F:31])[CH:3]=1

Participants

8

Reactant 4

HCID 5987Sulfamic AcidHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 866779482-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 712800452-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidYield 103.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(6-Chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (255 mg, 0.55 mmol) was dissolved in THF (8.3 ml) and water (2.8 ml). Sulfamic acid (517 mg, 5.3 mmol) was added. The reaction flask was cooled in an ice/water bath and a solution of sodium chlorite (104 mg, 1.15 mmol) and potassium phosphate monobasic (1.45 g, 10.6 mmol) in water (8 ml) was slowly added. After 1 h the reaction mixture was poured into ethyl acetate and water. The layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed with water and sodium chloride solution, and dried over sodium sulfate. Evaporation of the solvent gave 270 mg of 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as a light yellow solid. (M+H)+=476.

Workup

  1. temperatureThe reaction flask was cooled in an ice/water bath
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted once more with ethyl acetate
  4. washThe combined organic layers were washed with water and sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. customEvaporation of the solvent

Sources & evidence

ORD record
ord-977e78ca05814dedb4d35600e911bbca
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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