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

HRID 246268Notes

Reaction equation

HRID 246268 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[N:21]=[C:22]4[C:28]([CH:29]=[O:30])=[CH:27][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:23]4=[N:24][CH:25]=3)=[N:7][N:8]2[CH2:11][C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][CH:3]=1.S(=O)(=O)([OH:41])N.Cl([O-])=O.[Na+].P([O-])(O)(O)=O.[K+]>C1COCC1.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]3[N:21]=[C:22]4[C:28]([C:29]([OH:41])=[O:30])=[CH:27][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:23]4=[N:24][CH:25]=3)=[N:7][N:8]2[CH2:11][C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 5987Sulfamic AcidHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 866779702-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 712800952-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidYield 95.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In a 50 ml round-bottomed flask, 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (265 mg, 0.49 mmol) was dissolved in THF (10 ml) and water (2 ml). The yellow solution was cooled to 0° C. and sulfamic acid (287 mg, 2.95 mmol) was added. Then, a solution of sodium chlorite (80%, 76 mg, 0.67 mmol) and potassium dihydrogen phosphate (803 mg, 5.9 mmol) in water (6 ml) was added dropwise via pipette. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was triturated with hexanes/ethyl acetate to afford 259 mg (95%) of 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as a light yellow powder.

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. additionThe reaction mixture was diluted with water
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was triturated with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-dddae2411ad44dc9ba975eaf6c427c28
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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