3-Pyridine aldoxime → di(tert-butyl) 2-propyl-1-[3-(3-pyridin-3-ylisoxazol-5-yl)propyl]-6,7,8,9-tetrahydro-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate

HRID 1984482Notes

Reaction equation

HRID 1984482 reaction equation
ClN1C(=O)CCC1=O.[N:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]=[N:16][OH:17])[CH:10]=1.[CH2:18]([C:23]1[N:24]([CH2:51][CH2:52][CH3:53])[N:25]=[C:26]2[C:35]=1[C:34]1[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=1[N:28]=[C:27]2[N:36]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:19][CH2:20][C:21]#[CH:22].C(N(CC)CC)C>C1COCC1.ClCCl>[CH2:51]([N:24]1[C:23]([CH2:18][CH2:19][CH2:20][C:21]2[O:17][N:16]=[C:15]([C:11]3[CH:10]=[N:9][CH:14]=[CH:13][CH:12]=3)[CH:22]=2)=[C:35]2[C:26]([C:27]([N:36]([C:44]([O:46][C:47]([CH3:48])([CH3:50])[CH3:49])=[O:45])[C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])=[N:28][C:29]3[CH2:30][CH2:31][CH2:32][CH2:33][C:34]=32)=[N:25]1)[CH2:52][CH3:53]

Participants

7

Reactant 4

HCID 6943-Pyridine aldoximeHCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 86604925di(tert-butyl) 1-pent-4-ynyl-2-propyl-6,7,8,9-tetrahydro-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate

Product 1

HCID 66958831di(tert-butyl) 2-propyl-1-[3-(3-pyridin-3-ylisoxazol-5-yl)propyl]-6,7,8,9-tetrahydro-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonateYield 21.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Under a nitrogen atmosphere, N-chlorosuccinimide (2.1 g, 16 mmol) was added to a solution of 3-pyridine aldoxime (2.0 g, 16 mmol) in THF (10 mL). The solution was stirred at ambient temperature for 4 hours. A solution of di(tert-butyl) 1-pent-4-ynyl-2-propyl-6,7,8,9-tetrahydro-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate (4.00 g, 8.05 mmol), prepared as described in Example 615, and anhydrous triethylamine (2.5 mL, 18 mmol) in THF (10 mL) was added and the reaction solution was heated at 60° C. for 18 hours. The reaction solution was concentrated under reduced pressure to provide a black oil. The oil was dissolved in dichloromethane, washed sequentially with potassium carbonate, water, and brine, dried over sodium sulfate, and filtered. The filtrate was purified by column chromatography (silica gel, elution with a gradient of 20-80% ethyl acetate in hexanes) to provide 1.0877 g of di(tert-butyl) 2-propyl-1-[3-(3-pyridin-3-ylisoxazol-5-yl)propyl]-6,7,8,9-tetrahydro-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate.

Workup

  1. additionwas added
  2. temperaturethe reaction solution was heated at 60° C. for 18 hours
  3. concentrationThe reaction solution was concentrated under reduced pressure
  4. customto provide a black oil
  5. washwashed sequentially with potassium carbonate, water, and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customThe filtrate was purified by column chromatography (
  9. washsilica gel, elution with a gradient of 20-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-523e1a89e1874785854c5491cf7d7c2d
Source dataset
uspto-grants-2009_06
Patent number
US07544697B2

Reaction notes

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