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

HRID 887809Notes

Reaction equation

HRID 887809 reaction equation
[NH2:1][CH2:2][CH2:3][CH:4]1[C:8]2[C:9]3[N:10]([N:13]=[C:14]([CH3:21])[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:63](OC(=O)C)(=[O:65])[CH3:64]>O1CCCC1.O>[CH3:16][C:15]1[C:14]([CH3:21])=[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:63](=[O:65])[CH3:64])[C:8]=3[C:9]=12

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 62649Sodium sulfate decahydrateHCID 59145868ethyl 9-(2-aminoethyl)-2-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridine-1-carboxylateHCID 86583787Diisobutylaluminumhydride toluene

Product 1

HCID 59145848N-[2-(1,2-dimethyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridin-9-yl)ethyl]acetamideYield 34.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 9-(2-aminoethyl)-2-methyl-8,9-dihydro-7H-cyclopenta[c]pyrazolo[1,5-a]pyridine-1-carboxylate (75.0 mg, 0.261 mmol) in tetrahydrofuran (2.6 mL) was added 1.5M diisobutylaluminum hydride toluene solution (2.1 mL, 3.2 mmol) at room temperature, and the mixture was stirred for 3 hr. Sodium sulfate decahydrate (2.1 g) was added and the mixture was filtered through celite. The filtrate was concentrated under reduced pressure. To a mixture of the residue and triethylamine (54.6 μL, 0.392 mmol) in tetrahydrofuran (2.5 mL) was added acetic anhydride (37.0 μL, 0.391 mmol) under ice-cooling, and the mixture was stirred at room temperature for 30 min. Water (70 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→10/90) and recrystallization (ethyl acetate/diisopropyl ether) to give the title compound (24.4 mg, yield 34%).

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 30 min
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90) and recrystallization (ethyl acetate/diisopropyl ether)

Sources & evidence

ORD record
ord-bd9bfb72225f488eb530392e86d7c21d
Source dataset
uspto-grants-2012_08
Patent number
US08247429B2

Reaction notes

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