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

HRID 924404Notes

Reaction equation

HRID 924404 reaction equation
[C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].[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:1]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][CH2:2]1)(=[O:7])[CH3:6]

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 acetic anhydride (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 (270.0 mg, 0.7135 mmol) was sealed and heated at 90° C. for 1 h, then allowed to cool. After cooling, the excess acetic anhydride was removed under reduced pressure, the residue was dissolved in DCM, then poured into ice cold Na2CO3. The mixture was extracted twice with DCM, the combined extracts were dried, filtered and concentrated under reduced pressure to give the crude product, which was purified by preparative LCMS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with NH4OH) to provide the sub-title compound as yellow powder (65 mg, 22%). LCMS calc. for C20H29N4O6 (M+H)+: m/z=421.4. Found: 421.3.

Workup

  1. customwas sealed
  2. temperatureto cool
  3. temperatureAfter cooling
  4. customthe excess acetic anhydride was removed under reduced pressure
  5. dissolutionthe residue was dissolved in DCM
  6. additionpoured into ice cold Na2CO3
  7. extractionThe mixture was extracted twice with DCM
  8. customthe combined extracts were dried
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give the crude product, which
  12. customwas purified by preparative LCMS (pH=10 method
  13. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with NH4OH)

Sources & evidence

ORD record
ord-3cd51815846e44a880f84a6b7bd72540
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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