Ammonia → HCID 136336857, compound

HRID 69129Notes

Reaction equation

HRID 69129 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH2:6][CH2:5]2.C[Al](C)C.[CH:15]1([N:20]2[C:32]3[C:31]4[CH:30]=[CH:29][C:28]([C:33](OC)=[O:34])=[CH:27][C:26]=4[NH:25][C:24](=[O:37])[C:23]=3[CH:22]=[N:21]2)[CH2:19][CH2:18][CH2:17][CH2:16]1.Cl.N>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:33]([C:28]1[CH:29]=[CH:30][C:31]3[C:32]4[N:20]([CH:15]5[CH2:16][CH2:17][CH2:18][CH2:19]5)[N:21]=[CH:22][C:23]=4[C:24](=[O:37])[NH:25][C:26]=3[CH:27]=1)=[O:34])[CH2:6][CH2:5]2

Participants

9

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 1175965-ChloroindolineHCID 16682925TrimethylaluminumHCID 136336853HCID 136336853, compound

Product 1

HCID 136336857HCID 136336857, compoundYield 46.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Under a nitrogen atmosphere, to a solution of 148 mg of 5-chloroindoline in 1 mL of toluene was added 0.54 mL of a 1.8 M trimethylaluminum solution in toluene at 0° C., followed by stirring at room temperature for 2 hours (solution A). Under a nitrogen atmosphere, to a mixture of 100 mg of methyl 1-cyclopentyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline-7-carboxylate and 3 mL of toluene was added the solution A, followed by stirring at 70° C. for 8 hours. After cooling to room temperature, to the reaction mixture was added diluted hydrochloric acid, and the mixture was poured into a mixture of water and ethyl acetate. The pH was adjusted to 10 with 28% aqueous ammonia. The insoluble material was separated by filtration. The aqueous layer was separated, the organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform/methanol=100/0-92/8) to obtain 65 mg of 7-[(5-chloro-2,3-dihydro-1H-indol-1-yl)carbonyl]-1-cyclopentyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one as white powder.

Workup

  1. temperatureAfter cooling to room temperature, to the reaction mixture
  2. customThe insoluble material was separated by filtration
  3. customThe aqueous layer was separated
  4. washthe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (chloroform/methanol=100/0-92/8)

Sources & evidence

ORD record
ord-31aa06c97af448a79e2c84322941a916
Source dataset
uspto-grants-2014_09
Patent number
US08822448B2

Reaction notes

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