Sulfamic Acid → 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

HRID 246378

Reaktionsgleichung

Reaktionsgleichung von HRID 246378
[F:1][CH:2]([F:33])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[N:8]=[C:7]2[C:14]1[N:15]=[C:16]2[C:22]([CH:23]=[O:24])=[CH:21][N:20]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:17]2=[N:18][CH:19]=1.S(=O)(=O)([OH:36])N.Cl([O-])=O.[Na+].OP([O-])(O)=O.[K+]>O1CCOCC1.O>[F:33][CH:2]([F:1])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[N:8]=[C:7]2[C:14]1[N:15]=[C:16]2[C:22]([C:23]([OH:36])=[O:24])=[CH:21][N:20]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:32])[CH3:31])[C:17]2=[N:18][CH:19]=1

Komponenten

7

Edukt 4

HCID 5987Sulfamic Acid2×HCID 516951Monobasic potassium phosphate2×HCID 23668197Sodium Chlorite2×HCID 866779762-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Produkt 1

HCID 712805312-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidAusbeute 57 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel4×HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a solution of 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (217 mg, 458 μmol) in dioxane (6.5 mL) and water (2 mL) at 0° C. was added sulfamic acid (267 mg, 2.75 mmol), followed by drop-wise addition of a solution of sodium chlorite (67.3 mg, 596 μmol) and KH2PO4 (748 mg, 5.5 mmol) in water (4.5 mL) via dropping funnel over 15 min. The ice bath was removed and the light yellow suspension was stirred at 25° C. for 18 h. THF (6.5 mL) added to the yellow suspension and reaction continued at 25° C. for 2 h, then sulfamic acid (267 mg, 2.75 mmol) was added followed by dropwise addition of sodium chlorite (67.3 mg, 596 μmol) and KH2PO4 (748 mg, 5.5 mmol) in 5 mL of water. After 2 h the mixture was diluted with water (20 mL) and extracted with dichloromethane (3×30 mL). The combined organic layers were dried (MgSO4) and evaporated. The light yellow solid residue was dissolved in dichloromethane/MeOH and dichloromethane evaporated to promote solid formation, the solid separated by filtration, rinsed with MeOH and hexanes then dried to give 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (127 mg, 259 μmol, 57%) as a light yellow solid. MS (M+H)+=490; 1H NMR (DMSO-d6) δ: 12.57 (br. s., 1H), 9.12 (s, 1H), 8.69 (s, 1H), 8.65 (d, J=2.3 Hz, 1H), 7.80 (d, J=9.1 Hz, 1H), 7.35 (dd, J=8.9, 2.5 Hz, 1H), 7.20 (t, J=74.8 Hz, 1H), 5.71 (s, 2H), 4.18 (s, 3H), 3.58 (t, J=7.9 Hz, 2H), 0.84 (t, J=7.9 Hz, 2H), −0.21-−0.01 (s, 9H).

Aufarbeitung

  1. customover 15 min
  2. customThe ice bath was removed
  3. additionTHF (6.5 mL) added to the yellow suspension and reaction
  4. waitcontinued at 25° C. for 2 h
  5. extractionextracted with dichloromethane (3×30 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. customevaporated
  8. dissolutionThe light yellow solid residue was dissolved in dichloromethane/MeOH
  9. customdichloromethane evaporated
  10. customthe solid separated by filtration
  11. washrinsed with MeOH and hexanes
  12. customthen dried

Quellen und Nachweise

ORD-Eintrag
ord-b2ffef7ca09649bdb64e56dfba1ac544
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

Verknüpfte Notizen

Wird geladen…