Acetic Anhydride → 4-{(3S)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-nitro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

HRID 1499449Notes

Reaction equation

HRID 1499449 reaction equation
[CH3:1][C:2]([O:4][C:5]([CH3:7])=[O:6])=O.[N+:8]([C:11]1[C:12]([N:21]2[CH2:26][CH2:25][CH2:24][C@H:23]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:22]2)=[C:13]2[CH2:20]CC[C:14]2=[N+:15]([O-])[CH:16]=1)([O-:10])=[O:9]>>[C:5]([O:4][CH:2]1[C:14]2=[N:15][CH:16]=[C:11]([N+:8]([O-:10])=[O:9])[C:12]([N:21]3[CH2:26][CH2:25][CH2:24][C@H:23]([NH:27][C:28]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:34])[CH2:22]3)=[C:13]2[CH2:20][CH2:1]1)(=[O:6])[CH3:7]

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 86726692tert-Butyl [(3S)-1-(3-nitro-1-oxido-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)piperidin-3-yl]carbamate

Product 1

HCID 867266934-{(3S)-3-[(tert-Butoxycarbonyl)amino]piperidin-1-yl}-3-nitro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetateYield 22%

Conditions

Temperature
90 °C

Procedure

A mixture of Ac2O (0.90 g, 8.8 mmol) and tert-butyl [(3S)-1-(3-nitro-1-oxido-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)piperidin-3-yl]carbamate (270 mg, 0.714 mmol) was sealed and heated at 90° C. for 1 h, then allowed to cool to room temperature. The excess Ac2O was removed under reduced pressure. The residue was dissolved in DCM, and then poured into ice cold aq. Na2CO3. The mixture was extracted with DCM twice. The combined extracts were dried, filtered and concentrated under reduced pressure to give a crude product, which was purified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min., eluting with a gradient of MeCN and water with 0.15% NH4OH) to provide the sub-title compound as a yellow powder (65 mg, 22%). LCMS calc. for C20H29N4O6 (M+H)+: m/z=421.2. Found: 421.3.

Workup

  1. customwas sealed
  2. temperatureto cool to room temperature
  3. customThe excess Ac2O was removed under reduced pressure
  4. dissolutionThe residue was dissolved in DCM
  5. additionpoured into ice cold aq. Na2CO3
  6. extractionThe mixture was extracted with DCM twice
  7. customThe combined extracts were dried
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give a crude product, which
  11. customwas purified by preparative LC-MS (XBridge™ preparative C18 5 μm 30×10 mm OBD™ column, flow rate 60 mL/min.
  12. washeluting with a gradient of MeCN and water with 0.15% NH4OH)

Sources & evidence

ORD record
ord-f6d8fd6c503f44468349fbe93ab66486
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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