Water → HCID 11660060, compound

HRID 1158819Notes

Reaction equation

HRID 1158819 reaction equation
C(N(CC)[CH:5]([CH3:7])[CH3:6])(C)C.COC([N:14]1[C:22]2[C:17](=[C:18]([NH:23][C:24]([O:26]N3C(=O)CCC3=O)=O)[CH:19]=[CH:20][CH:21]=2)[CH:16]=[N:15]1)=O.[OH2:34].C[N:36]([CH3:39])C=O>>[NH:14]1[C:22]2[C:17](=[C:18]([NH:23][C:24]([NH:36][CH2:39][CH:22]3[CH2:21][CH2:20][C:19]4[C:18](=[CH:17][CH:16]=[C:5]([CH3:6])[CH:7]=4)[O:34]3)=[O:26])[CH:19]=[CH:20][CH:21]=2)[CH:16]=[N:15]1

Participants

5

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 11313556methyl 4-({[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}amino)-1H-indazole-1-carboxylate

Product 1

HCID 11660060HCID 11660060, compound

Procedure

A reaction mixture of 0.4 g (2.3 mMol) of the compound from example 104D in 4 mls of N,N-dimethylformamide, 0.85 mls (4.8 mMol) of N,N-diisopropylethylamine and 0.8 g (2.3 mMol) of the compound from example 24D was stirred at ambient temperature for 18 hours. 50 mls of water was added to the reaction and the precipitate collected by filtration. The precipitate was solubilized in ethyl acetate and the organic phase extracted with water and saturated NaCl. The organic phase was dried with MgSO4, filtered and the solvent evaporated. 2 mls of 5N NaOH in methanol was added to the residue and stirred at room temperature for 1 hour. 100 mls of ethyl acetate was added and the organic phase extracted with water and saturated NaCl. The organic phase was dried with MgSO4, filtered and the solvent removed, and the residue purified by flash chromatography using a gradient from dichloromethane to 10% methanol in dichloromethane with a few drops of NH4OH as the solvent system to provide the titled compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.98 (s, 1H) 8.78 (s, 1H) 8.09 (s, 1H) 7.64 (d, J=7.12 Hz, 1H) 7.20 (t, J=7.97 Hz, 1H) 7.05 (d, J=8.14 Hz, 1H) 6.84-6.91 (m, 2H) 6.59-6.71 (m, 2H) 4.02-4.11 (m, 1H) 3.36-3.51 (m, 2H) 2.74-2.88 (m, 1H) 2.62-2.74 (m, 1H) 2.19 (s, 3H) 1.91-2.04 (m, 1H) 1.61-1.76 (m, 1H). MS ESI m/z 337.1 (M+H)+.

Workup

  1. filtrationthe precipitate collected by filtration
  2. extractionthe organic phase extracted with water and saturated NaCl
  3. dry with materialThe organic phase was dried with MgSO4
  4. filtrationfiltered
  5. customthe solvent evaporated
  6. addition2 mls of 5N NaOH in methanol was added to the residue
  7. stirringstirred at room temperature for 1 hour
  8. addition100 mls of ethyl acetate was added
  9. extractionthe organic phase extracted with water and saturated NaCl
  10. dry with materialThe organic phase was dried with MgSO4
  11. filtrationfiltered
  12. customthe solvent removed
  13. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-7762e6c7744749fc82721eb555bf6032
Source dataset
uspto-grants-2010_10
Patent number
US07812019B2

Reaction notes

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