Propylphosphonic anhydride → HCID 68753292, compound

HRID 1038826Notes

Reaction equation

HRID 1038826 reaction equation
[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]([CH:21]=O)=[N:9][N:10]2[CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])=[CH:6][CH:5]=1)([O-:3])=[O:2].Cl.[NH2:24]O.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:21]#[N:24])=[N:9][N:10]2[CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 111923Propylphosphonic anhydrideHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 86665092HCID 86665092, compound

Product 1

HCID 68753292HCID 68753292, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

6-Nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carbaldehyde (0.2 g, 0.622 mmol, prepared using N from 6-nitro-1H-indazole-3-carbaldehyde [Chempacific]), hydroxylamine hydrochloride (0.048 g, 0.68 mmol), and TEA (0.095 mL, 0.68 mmol) were combined in DMF (1.24 mL) in a sealed vial. 2,4,6-Tripropyl-[1,3,5,2,4,6]trioxatriphosphinane 2,4,6-trioxide (50% solution in DMF, 0.400 mL, 0.684 mmol) was added and the mixture was heated at about 100° C. for about 6 h. The mixture was allowed to cool to rt. EtOAc (15 mL) and an aqueous solution of saturated NaHCO3 (5 mL) were added and the layers separated. The aqueous layer was extracted with EtOAc (1×5 mL). The combined extracts were washed with 5% aqueous LiCl (3×10 mL). The combined extracts were washed with brine (10 mL), dried over MgSO4, filtered and evaporated under vacuum. The sample was re-dissolved in DCM and dry loaded onto silica gel (2 mL). The residue was purified by column chromatography (25 g silica gel) eluting with 10 to 25% EtOAc/heptane to provide 6-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carbonitrile (0.132 g, 67%): 1H NMR (400 MHz, DMSO-d6) δ 9.02 (dd, J=1.5, 1.1 Hz, 1H), 8.22-8.21 (m, 2H), 6.05 (s, 2H), 3.60-3.54 (m, 2H), 0.83-0.78 (m, 2H), −0.12 (s, 9H)

Workup

  1. temperatureto cool to rt
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with EtOAc (1×5 mL)
  4. washThe combined extracts were washed with 5% aqueous LiCl (3×10 mL)
  5. washThe combined extracts were washed with brine (10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated under vacuum
  9. dissolutionThe sample was re-dissolved in DCM
  10. customdry
  11. customThe residue was purified by column chromatography (25 g silica gel)
  12. washeluting with 10 to 25% EtOAc/heptane

Sources & evidence

ORD record
ord-fecd12da22af4d9bb5f9c00c56a1a348
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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