Water → 3-(7-carboxy-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide

HRID 246408Notes

Reaction equation

HRID 246408 reaction equation
[CH3:1][N:2]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[C:4]([C:11]2[N:12]=[C:13]3[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]3=[N:15][CH:16]=2)=[N:3]1.S(=O)(=O)([OH:32])N.Cl([O-])=O.[Na+].OP([O-])(O)=O.[K+].[OH2:45]>O1CCOCC1>[C:20]([C:19]1[C:13]2[C:14](=[N:15][CH:16]=[C:11]([C:4]3[C:5]4[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=4[N:2]([CH3:1])[N+:3]=3[O-:32])[N:12]=2)[N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:18]=1)([OH:21])=[O:45]

Participants

7

Reactant 5

HCID 962Water2×HCID 5987Sulfamic AcidHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 866779782-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 712802803-(7-carboxy-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxideYield 51.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

To a yellow-brown solution of 2-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (265 mg, 644 μmol) in dioxane (14.0 mL) and water (4 mL) at 0° C. (became a suspension after cooling) was added sulfamic acid (375 mg, 3.86 mmol, Eq: 6.00), followed by drop-wise addition of a solution of sodium chlorite (94.6 mg, 837 μmol.30) and KH2PO4 (1.05 g, 7.73 mmol2.00) 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. Mixture diluted with water (50 mL) and extracted with 5% MeOH in dichloromethane (3×40 mL). The combined organic layers were dried (MgSO4) and evaporated. Light yellow solid residue was dissolved in dichloromethane and purified by chromatography (spherical silica 20-45 μm, 50 g, Versaflash Supelco) eluting with 0 to 5% MeOH in dichloromethane. Pure compound dissolved in dichloromethane, added some cyclohexane and dichloromethane evaporated to promote solid formation, solid separated by filtration, rinsed with hexanes and dried to give 3-(7-carboxy-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (147 mg, 331 μmol, 51.5%) as a white solid. MS (M+H)+=444 (100% purity); 1H NMR (CDCl3) δ: 9.19 (s, 1H), 8.45 (s, 1H), 5.76 (s, 2H), 3.58-3.71 (m, 2H), 3.50 (s, 3H), 2.39-2.55 (m, 2H), 2.24-2.38 (m, 2H), 1.99-2.22 (m, 4H), 0.91-1.07 (m, 2H), 0.00 (s, 9H).

Workup

  1. customat 0° C.
  2. temperatureafter cooling)
  3. customover 15 min
  4. customThe ice bath was removed
  5. additionMixture diluted with water (50 mL)
  6. extractionextracted with 5% MeOH in dichloromethane (3×40 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. customevaporated
  9. dissolutionLight yellow solid residue was dissolved in dichloromethane
  10. custompurified by chromatography (spherical silica 20-45 μm, 50 g, Versaflash Supelco)
  11. washeluting with 0 to 5% MeOH in dichloromethane
  12. dissolutionPure compound dissolved in dichloromethane
  13. additionadded some cyclohexane and dichloromethane
  14. customevaporated
  15. customseparated by filtration
  16. washrinsed with hexanes
  17. customdried

Sources & evidence

ORD record
ord-39c8a6e2c2c946ab849007601c5cef35
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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