Water → tert-butyl 4-(2-(7-nitro-2,3-dihydro-1H-pyrazolo[1,5-a]imidazol-1-yl)ethyl)piperidine-1-carboxylate

HRID 2089431Notes

Reaction equation

HRID 2089431 reaction equation
[H-].[Na+].[N+:3]([C:6]1[CH:7]=[N:8][N:9]2[CH2:13][CH2:12][NH:11][C:10]=12)([O-:5])=[O:4].S(O[CH2:25][CH2:26][CH:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1)(C1C=CC(C)=CC=1)(=O)=O.O>C1COCC1>[N+:3]([C:6]1[CH:7]=[N:8][N:9]2[CH2:13][CH2:12][N:11]([CH2:25][CH2:26][CH:27]3[CH2:28][CH2:29][N:30]([C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])[CH2:31][CH2:32]3)[C:10]=12)([O-:5])=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydride2×HCID 21936070N-Boc-4-[2-(4-Toluenesulfonyloxy)ethyl]piperidineHCID 1358007277-nitro-2,3-dihydro-1H-imidazo[1,2-b]pyrazole

Product 1

HCID 58464885tert-butyl 4-(2-(7-nitro-2,3-dihydro-1H-pyrazolo[1,5-a]imidazol-1-yl)ethyl)piperidine-1-carboxylateYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil, 39 mg, 0.97 mmol) was added portionwise to a stirred solution of 7-nitro-2,3-dihydro-1H-pyrazolo[1,5-a]imidazole (0.125 g, 0.81 mmol) in anhydrous THF (10 mL) at room temperature under a nitrogen atmosphere. The mixture was stirred for 10 min. before a solution of tert-butyl 4-(2-(tosyloxy)ethyl)piperidine-1-carboxylate (0.31 g, 0.81 mmol) in THF (5 mL) was added portionwise over 10 min. The reaction was stirred for 6 hr at room temperature followed by 18 hr at 50° C. Further sodium hydride (60% dispersion in mineral oil, 39 mg, 0.97 mmol) was added and stirring continued at 60° C. for a further 24 h. The reaction was cooled and water was added dropwise. The mixture was extracted with EtOAc and the combined organics were dried over MgSO4 and concentrated under reduced pressure. The crude residue was purified via silica gel chromatography (0-100% EtOAc/isohexane) to give tert-butyl 4-(2-(7-nitro-2,3-dihydro-1H-pyrazolo[1,5-a]imidazol-1-yl)ethyl)piperidine-1-carboxylate as a yellow oil (50 mg, 17%). 1H NMR (400 MHz, CDCl3) δ 7.83 (s, 1H), 4.24-4.16 (m, 2H), 4.25-3.97 (m, 2H), 3.83-3.77 (s, 2H), 3.27 (s, 2H), 3.22 (t, J=6.8 Hz, 2H), 2.72-2.62 (s, 2H), 1.73-1.65 (m, 3H), 1.46-1.44 (m, 9H) 1.40-1.05 (m, 2H)

Workup

  1. additionwas added portionwise over 10 min
  2. waitfollowed by 18 hr at 50° C
  3. stirringstirring
  4. waitcontinued at 60° C. for a further 24 h
  5. temperatureThe reaction was cooled
  6. extractionThe mixture was extracted with EtOAc
  7. dry with materialthe combined organics were dried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue was purified via silica gel chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-e2dee70106984043bf92b63f466fd6d8
Source dataset
uspto-grants-2013_05
Patent number
US08436001B2

Reaction notes

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