1,1'-Carbonyldiimidazole → HCID 86700691, compound

HRID 1406872Notes

Reaction equation

HRID 1406872 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:13]([O:20][N:21]1[C:27](=[O:28])[N:26]2[CH2:29][C@H:22]1[CH2:23][CH2:24][C@H:25]2[C:30]1[O:31]C(C2CCNCC2)=N[N:34]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O/[N:42]=[C:43](\[CH:45]1[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH2:46]1)/N>CN(C=O)C.CCOC(C)=O>[CH2:13]([O:20][N:21]1[C:27](=[O:28])[N:26]2[CH2:29][C@H:22]1[CH2:23][CH2:24][C@H:25]2[C:30]1[O:31][N:42]=[C:43]([CH:45]2[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH2:46]2)[N:34]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 59404825HCID 59404825, compoundHCID 86700689HCID 86700689, compound

Product 1

HCID 86700691HCID 86700691, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

CDI (511.3 mg, 3.1 mmol) was added to a solution of crude (2S,5R)-6-(benzyloxy)-2-(5-(piperidin-4-yl)-1,3,4-oxadiazol-2-yl)-1,6-diazabicyclo[3.2.1]octan-7-one (726 mg, 2.6 mmol) in DMF (15 mL). The mixture was stirred at rt for 1 h, then, (E)-tert-butyl 4-(N′-hydroxycarbamimidoyl)piperidine-1-carboxylate (631.8 mg, 2.6 mmol) was added at rt. The mixture was stirred at rt for 2 hrs, and then stirred at 50° C. for another 6 hrs. The mixture was diluted with EtOAc (150 mL) and washed with 1 M HCl (2×), water (2×), and saturated sodium chloride (2×), dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography (1:5 to 1:1 EtOAc/hexanes) to give tert-butyl 4-(5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,2,4-oxadiazol-3-yl)piperidine-1-carboxylate (968 mg, 76%) as a white solid. ESI-MS (EI+, m/z): 506.2 [M+Na]+. 1H-NMR (400 MHz, CDCl3): δ 7.47-7.36 (m, 5H), 4.99-4.94 (m, 2H), 4.73 (d, J=6.0 Hz, 1H), 3.93 (d, J=9.6 Hz, 1H), 3.72 (s, 1H), 3.08-2.90 (m, 4H), 2.72 (d, J=9.6 Hz, 1H), 2.15 (dd, J=12.0, 5.2 Hz, 1H), 2.09-1.93 (m, 5H), 1.85-1.79 (m, 1H), 1.59-1.50 (m, 2H), 1.40 (s, 9H).

Workup

  1. stirringThe mixture was stirred at rt for 2 hrs
  2. stirringstirred at 50° C. for another 6 hrs
  3. washwashed with 1 M HCl (2×), water (2×), and saturated sodium chloride (2×)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (1:5 to 1:1 EtOAc/hexanes)

Sources & evidence

ORD record
ord-9e2a0eb365cd477e8db5a15fc1d15324
Source dataset
uspto-grants-2014_12
Patent number
US08916709B2

Reaction notes

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