Carbonate Ion → 3-(1-{[7-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-8-yl]carbonyl}piperidin-4-yl)benzoic acid

HRID 69134

Reaction equation

HRID 69134 reaction equation
[CH3:1][C:2]1[C:3]([C:22]([OH:24])=O)=[CH:4][C:5]2[C:6]3[N:15]([CH:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[N:14]=[CH:13][C:7]=3[C:8](=[O:12])[NH:9][C:10]=2[CH:11]=1.Cl.[NH:26]1[CH2:31][CH2:30][CH:29]([C:32]2[CH:33]=[C:34]([CH:39]=[CH:40][CH:41]=2)[C:35]([O:37]C)=[O:36])[CH2:28][CH2:27]1.ON1C2C=CC=CC=2N=N1.N=C=N.C(=O)([O-])[O-].[N-]=C=O>CN(C=O)C.C(N(CC)CC)C>[CH3:1][C:2]1[C:3]([C:22]([N:26]2[CH2:31][CH2:30][CH:29]([C:32]3[CH:33]=[C:34]([CH:39]=[CH:40][CH:41]=3)[C:35]([OH:37])=[O:36])[CH2:28][CH2:27]2)=[O:24])=[CH:4][C:5]2[C:6]3[N:15]([CH:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[N:14]=[CH:13][C:7]=3[C:8](=[O:12])[NH:9][C:10]=2[CH:11]=1

Participants

9

Reactant 6

HCID 19660Carbonate IonHCID 757711-HydroxybenzotriazoleHCID 105034IsocyanateHCID 160435CarbodiimideHCID 44607825Methyl 3-(piperidin-4-yl)benzoate hydrochlorideHCID 1363368547-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline-8-carboxylic acid

Product 1

HCID 1363368633-(1-{[7-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-8-yl]carbonyl}piperidin-4-yl)benzoic acidYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a mixture of 8.2 mg of 7-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline-8-carboxylic acid, 7.7 mg of methyl 3-piperidin-4-yl-benzoate monohydrochloride, 3.4 mg of 1-hydroxybenzotriazole, 7.0 μL of triethylamine, and 1.0 mL of DMF was added 100 mg of PS-Carbodiimide (Biotage), followed by stirring at room temperature overnight. To the reaction mixture were added 75 mg of MP-Carbonate (Biotage), 50 mg of PS-Isocyanate (Biotage), and 0.5 mL of DMF at room temperature, followed by stirring for 2 hours. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. To the obtained residue were added 0.5 mL of methanol, 0.5 mL of tetrahydrofuran, and 0.5 mL of a 1 M aqueous sodium hydroxide solution, followed by stirring at room temperature overnight. To the reaction mixture was added 0.5 mL of 1 M hydrochloric acid and the solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC (methanol/0.1% aqueous formic acid solution) to obtain 5.8 mg of 3-(1-{[7-methyl-4-oxo-1-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinolin-8-yl]carbonyl}piperidin-4-yl)benzoic acid.

Workup

  1. stirringby stirring for 2 hours
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionTo the obtained residue were added 0.5 mL of methanol, 0.5 mL of tetrahydrofuran, and 0.5 mL of a 1 M aqueous sodium hydroxide solution
  5. stirringby stirring at room temperature overnight
  6. additionTo the reaction mixture was added 0.5 mL of 1 M hydrochloric acid
  7. customthe solvent was evaporated under reduced pressure
  8. customThe obtained residue was purified by preparative HPLC (methanol/0.1% aqueous formic acid solution)

Sources & evidence

ORD record
ord-550a46d6cb4e400e8ca14ebad9e37f34
Source dataset
uspto-grants-2014_09
Patent number
US08822448B2

Linked notes

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