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

HRID 245820

Reaktionsgleichung

Reaktionsgleichung von HRID 245820
[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])=[CH:4][CH:3]=1.S(=O)(=O)([OH:33])N.Cl([O-])=O.[Na+].P([O-])(O)(O)=O.[K+]>O1CCOCC1.O>[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: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

Komponenten

7

Edukt 4

HCID 5987Sulfamic AcidHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 715755472-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Produkt 1

HCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidAusbeute 84,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

In a round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (412 mg, 0.93 mmol) was suspended in 1,4-dioxane (15 ml) and water (3 ml). The suspension was cooled to 0° C. and sulfamic acid (543 mg, 5.59 mmol) was added. Then, a solution of sodium chlorite (80%, 137 mg, 1.21 mmol) and potassium dihydrogen phosphate (1.52 g, 11.2 mmol) in water (9 ml) was added via dropping funnel over ˜20 min. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 3 h. THF (15 ml) was added and the reaction mixture was stirred at room temperature for an additional 3 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 ethyl acetate/hexanes to afford 358 mg (84%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as a light yellow powder.

Aufarbeitung

  1. customover ˜20 min
  2. additionAfter the addition
  3. customthe ice bath was removed
  4. additionTHF (15 ml) was added
  5. stirringthe reaction mixture was stirred at room temperature for an additional 3 h
  6. additionThe reaction mixture was diluted with water
  7. extractionextracted with EtOAc (2×)
  8. washThe combined organic layers were washed with water and brine
  9. dry with materialthen dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was triturated with ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-2e83f65961a546378dca28a33ce367e8
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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