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

HRID 887813Notes

Reaction equation

HRID 887813 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 59145898ethyl (9S)-9-{2-[(tert-butoxycarbonyl)amino]ethyl}-2-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridine-1-carboxylate

Product 1

HCID 59145932N-{2-[(9S)-2-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridin-9-yl]ethyl}acetamideYield 75%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl (9S)-9-{2-[(tert-butoxycarbonyl)amino]ethyl}-2-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridine-1-carboxylate (140 mg, 0.361 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 (503 μL, 3.61 mmol) in tetrahydrofuran (3.6 mL) was added acetic anhydride (102 μL, 1.08 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 (69.7 mg, yield 75%, >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-116e48a3be64469bb7b53beee87c171a
Source dataset
uspto-grants-2012_08
Patent number
US08247429B2

Reaction notes

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