Pyridine → HCID 86701391, compound

HRID 870847Notes

Reaction equation

HRID 870847 reaction equation
[N:1]1([C:7](Cl)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.N1C=CC=CC=1.Cl.[CH2:17]([O:24][N:25]1[C:31](=[O:32])[N:30]2[CH2:33][C@H:26]1[CH2:27][CH2:28][C@H:29]2[C:34]([NH:36][NH2:37])=[O:35])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:17]([O:24][N:25]1[C:31](=[O:32])[N:30]2[CH2:33][C@H:26]1[CH2:27][CH2:28][C@H:29]2[C:34]([N:36]([C:7]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[O:8])[NH2:37])=[O:35])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 848104-Morpholinecarbonyl chlorideHCID 86701390HCID 86701390, compound

Product 1

HCID 86701391HCID 86701391, compoundYield 47.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

Morpholine-4-carbonyl chloride (297 mg, 1.99 mmol) was added dropwise over a period of 10 minutes to a solution of DMAP (24 mg, 0.199 mmol) and pyridine (0.16 mL, 1.99 mmol) in dry DCM (5 mL). The mixture was stirred at 0° C. for 20 minutes then, a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbohydrazide hydrochloride (0.65 g, 1.99 mmol) in dry DCM (2.0 mL) was added over a period of 10 minutes. The mixture was stirred at 0° C. for 15 min and was then allowed to warm to rt and was stirred overnight. The reaction mixture was diluted with DCM (10 mL), and washed with 1N HCl (10 mL), and saturated sodium chloride (10 mL), then was dried over Na2SO4 and concentrated. The crude product was purified by silica gel column chromatography (0 to 1:100 MeOH/DCM, containing 1% TEA) to give N-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl) morpholine-4-carbohydrazide (0.38 g, 47%) as a white solid. ESI-MS (EI+, m/z): 404.19 [M+H]+.

Workup

  1. stirringThe mixture was stirred at 0° C. for 15 min
  2. temperatureto warm to rt
  3. stirringwas stirred overnight
  4. washwashed with 1N HCl (10 mL), and saturated sodium chloride (10 mL)
  5. dry with materialwas dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel column chromatography (0 to 1:100 MeOH/DCM, containing 1% TEA)

Sources & evidence

ORD record
ord-2d378ae3881445719cab209c1f5bc985
Source dataset
uspto-grants-2015_03
Patent number
US08969570B2

Reaction notes

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