Sulfamic Acid → 2-[6-Chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

HRID 246112Notes

Reaction equation

HRID 246112 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:16]3[N:17]=[C:18]4[C:24]([CH:25]=[O:26])=[CH:23][N:22]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:19]4=[N:20][CH:21]=3)=[N:7][N:8]2[CH2:11][CH2:12][N:13]([CH3:15])[CH3:14])=[C:4]([F:35])[CH:3]=1.S(=O)(=O)([OH:38])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:16]3[N:17]=[C:18]4[C:24]([C:25]([OH:38])=[O:26])=[CH:23][N:22]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:32])[CH3:34])[C:19]4=[N:20][CH:21]=3)=[N:7][N:8]2[CH2:11][CH2:12][N:13]([CH3:15])[CH3:14])=[C:4]([F:35])[CH:3]=1

Participants

8

Reactant 4

HCID 5987Sulfamic AcidHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 866779502-[6-chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 712800772-[6-Chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidYield 110.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-[6-Chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (46 mg, 0.09 mmol) was dissolved in THF (1.3 ml) and water (0.4 ml) and sulfamic acid (83 mg, 0.85 mmol) was added. A solution of sodium chlorite (17 mg, 0.185 mmol) and potassium phosphate monobasic (232 mg, 1.7 mmol) in water (1.4 ml) was slowly added. After 1 h the reaction mixture was poured into ethyl acetate and water. The pH was adjusted to 6, the layers were separated and the aqueous layer was extracted five times with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated to give 53 mg of 2-[6-chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid.

Workup

  1. customthe layers were separated
  2. extractionthe aqueous layer was extracted five times with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-b7224db3801f4679ae0e056183427d5d
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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