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

HRID 887806Notes

Reaction equation

HRID 887806 reaction equation
[NH2:1][CH2:2][CH2:3][CH:4]1[C:8]2[C:9]3[N:10]([N:13]=[CH:14][C:15]=3[C:16](OCC)=O)[CH:11]=[CH:12][C:7]=2[CH2:6][CH2:5]1.C1(C)C=CC=CC=1.[H-].C([Al+]CC(C)C)C(C)C.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+].C(N(CC)CC)C.[C:62](OC(=O)C)(=[O:64])[CH3:63]>O1CCCC1.O>[CH3:16][C:15]1[CH:14]=[N:13][N:10]2[CH:11]=[CH:12][C:7]3[CH2:6][CH2:5][CH:4]([CH2:3][CH2:2][NH:1][C:62](=[O:64])[CH3:63])[C:8]=3[C:9]=12

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 62649Sodium sulfate decahydrateHCID 59145841ethyl 9-(2-aminoethyl)-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridine-1-carboxylateHCID 86583787Diisobutylaluminumhydride toluene

Product 1

HCID 59145930N-[2-(1-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridin-9-yl)ethyl]acetamideYield 17.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 9-(2-aminoethyl)-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridine-1-carboxylate (45.0 mg, 0.165 mmol) in tetrahydrofuran (1.7 mL) was added 1.5M diisobutylaluminum hydride toluene solution (1.3 mL, 1.95 mmol) at room temperature, and the mixture was stirred for 3 hr. Sodium sulfate decahydrate (1.3 g) was added, and the mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. To a mixture of the residue and triethylamine (34.5 μL, 0.248 mmol) in tetrahydrofuran (1.7 mL) was added acetic anhydride (23.4 μL, 0.248 mmol) under ice-cooling, and the mixture was stirred at room temperature for 15 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) and recrystallization (ethyl acetate/diisopropyl ether) to give the title compound (7.3 mg, yield 17%).

Workup

  1. filtrationthe mixture was filtered through celite
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. temperaturecooling
  4. stirringthe mixture was stirred at room temperature for 15 min
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→5/95) and recrystallization (ethyl acetate/diisopropyl ether)

Sources & evidence

ORD record
ord-527bec76b41c4510b91b4f3f6bbe65f0
Source dataset
uspto-grants-2012_08
Patent number
US08247429B2

Reaction notes

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