Oxalyl chloride → 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(3-trifluoromethyl-phenyl)-cyclopropyl]-amide

HRID 2172982Notes

Reaction equation

HRID 2172982 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[N:14][CH:15]=[C:16]([C:17]([OH:19])=O)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.Cl.[F:27][C:28]([F:40])([F:39])[C:29]1[CH:30]=[C:31]([C:35]2([NH2:38])[CH2:37][CH2:36]2)[CH:32]=[CH:33][CH:34]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O>[F:27][C:28]([F:39])([F:40])[C:29]1[CH:30]=[C:31]([C:35]2([NH:38][C:17]([C:16]3[C:11]4[CH:10]=[N:9][N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[C:12]=4[CH:13]=[N:14][CH:15]=3)=[O:19])[CH2:36][CH2:37]2)[CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chloride2×HCID 81531DiisopropylethylamineHCID 592781371-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acidHCID 684727951-(3-(Trifluoromethyl)phenyl)cyclopropanamine hydrochloride

Product 1

HCID 529169711-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(3-trifluoromethyl-phenyl)-cyclopropyl]-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (40.0 mg, 0.156 mmol) in methylene chloride (1 mL) is added oxalyl chloride (14 μL, 0.16 mmol) dropwise. After 10 minutes, a drop of N,N-dimethylformamide is added and the suspension is stirred at room temperature. After 60 minutes, an additional portion of oxalyl chloride (14 μL, 0.16 mmol) and a drop of N,N-dimethylformamide are added. After stirring for 30 minutes, the solvent is removed in vacuo; the residue is suspended in methylene chloride (1 mL) and concentrated in vacuo. The residue is dried under vacuum for 30 minutes, suspended in methylene chloride (1 mL) and added to a solution of 1-(3-trifluoromethyl-phenyl)-cyclopropylamine hydrochloride (74.1 mg, 0.312 mmol) and N,N-diisopropylethylamine (0.080 mL, 0.46 mmol) in methylene chloride (500 μL). After shaking at room temperature for 15 hours, the reaction is quenched with methanol (500 μL) and concentrated. The residue is purified by reverse phase HPLC using a Water BEH column (2.1×50 mm C18 1.7 μM) and a gradient of 10-95% acetonitrile in water containing 0.05% formic acid to afford the title compound.

Workup

  1. waitAfter 60 minutes
  2. stirringAfter stirring for 30 minutes
  3. customthe solvent is removed in vacuo
  4. concentrationconcentrated in vacuo
  5. customThe residue is dried under vacuum for 30 minutes
  6. stirringAfter shaking at room temperature for 15 hours
  7. customthe reaction is quenched with methanol (500 μL)
  8. concentrationconcentrated
  9. customThe residue is purified by reverse phase HPLC

Sources & evidence

ORD record
ord-25d6fc6bede347d28b8a4d077113c645
Source dataset
uspto-grants-2015_06
Patent number
US09056858B2

Reaction notes

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