Water → N-{2-[(9R)-2-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridin-9-yl]ethyl}acetamide

HRID 887814Notes

Reaction equation

HRID 887814 reaction equation
C([O:5][C:6]([NH:8][CH2:9][CH2:10][C@@H:11]1[C:15]2[C:16]3[N:17]([N:20]=[C:21]([CH3:28])[C:22]=3C(OCC)=O)[CH:18]=[CH:19][C:14]=2[CH2:13][CH2:12]1)=O)(C)(C)C.[CH2:29](N(CC)CC)C.C(OC(=O)C)(=O)C.O>Cl.O1CCCC1>[CH3:28][C:21]1[CH:22]=[C:16]2[C:15]3[C@@H:11]([CH2:10][CH2:9][NH:8][C:6](=[O:5])[CH3:29])[CH2:12][CH2:13][C:14]=3[CH:19]=[CH:18][N:17]2[N:20]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 59145914ethyl (9R)-9-{2-[(tert-butoxycarbonyl)amino]ethyl}-2-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridine-1-carboxylate

Product 1

HCID 59145880N-{2-[(9R)-2-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridin-9-yl]ethyl}acetamideYield 96%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl (9R)-9-{2-[(tert-butoxycarbonyl)amino]ethyl}-2-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridine-1-carboxylate (135 mg, 0.348 mmol) in 12M hydrochloric acid (4 mL) was stirred at 100° C. for 3 days, and concentrated under reduced pressure. To a mixture of the residue and triethylamine (485 μL, 3.48 mmol) in tetrahydrofuran (3.5 mL) was added acetic anhydride (98.7 μL, 1.04 mmol) under ice-cooling, and the mixture was stirred at room temperature for 10 min. Water (50 μL) was added, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→5/95) to give the title compound (86.0 mg, yield 96%, 99.9% ee). The enantiomer excess (ee) was measured by high performance liquid chromatography (column: CHIRALPAK AD-H mm ID×250 mm L, manufactured by Dicel Chemical Industries, Ltd.), mobile phase: hexane/ethanol=95/5, flow rate: 1.0 mL/min, column temperature: 30° C., sample concentration: 0.5 mg/mL (hexane/ethanol=95/5), injection volume: 10 μL).

Workup

  1. concentrationconcentrated under reduced pressure
  2. temperaturecooling
  3. stirringthe mixture was stirred at room temperature for 10 min
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→5/95)

Sources & evidence

ORD record
ord-7cdb89e4985b4f27aa05033cf313b276
Source dataset
uspto-grants-2012_08
Patent number
US08247429B2

Reaction notes

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