Pyridine → 2-[2-(3-chloro-pyridin-2-yl)-5-hydroxy-2H-pyrazol-3-yl]-10-methyl-3-oxa-1,8-diaza-phenanthren-4-one

HRID 245652Notes

Reaction equation

HRID 245652 reaction equation
[NH2:1][C:2]1[C:11]([CH3:12])=[CH:10][C:9]2[N:8]=[CH:7][CH:6]=[CH:5][C:4]=2[C:3]=1[C:13]([OH:15])=[O:14].[Cl:16][C:17]1[C:18]([N:23]2[C:27]([C:28](O)=O)=[CH:26][C:25](C(F)(F)F)=[N:24]2)=[N:19][CH:20]=[CH:21][CH:22]=1.N1C=CC=CC=1.CS(Cl)(=O)=[O:43]>C1COCC1>[Cl:16][C:17]1[C:18]([N:23]2[C:27]([C:28]3[O:14][C:13](=[O:15])[C:3]4[C:4]5[C:9](=[N:8][CH:7]=[CH:6][CH:5]=5)[CH:10]=[C:11]([CH3:12])[C:2]=4[N:1]=3)=[CH:26][C:25]([OH:43])=[N:24]2)=[N:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 113921841-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acidHCID 579901086-Amino-7-methyl-quinoline-5-carboxylic acid

Product 1

HCID 1784223002-[2-(3-chloro-pyridin-2-yl)-5-hydroxy-2H-pyrazol-3-yl]-10-methyl-3-oxa-1,8-diaza-phenanthren-4-oneYield 50.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 282 mg (1.39 mmol) of 6-amino-7-methyl-quinoline-5-carboxylic acid in 11 mL of anhydrous THF is added 407 mg (1.39 mmol) of 2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid followed by 560 μL (7.0 mmol) of pyridine. The mixture is stirred at ambient temperature during 30 minutes. Then the suspension is cooled to 0° C. and 430 μL (5.5 mmol) of methanesulfonyl chloride are added dropwise. The mixture is stirred at ambient temperature for 48 hours. Then the solvent is evaporated and the residue is sequentially triturated and filtrated with ethyl acetate and with a minimum of cold water. Purification of the residue by flash chromatography (SiO2, heptane/ethyl acetate 1:2) affords 286 mg (45%) of the product as a yellowish solid; LC/MS:468/460 (M+H)+.

Workup

  1. temperatureThen the suspension is cooled to 0° C.
  2. stirringThe mixture is stirred at ambient temperature for 48 hours
  3. customThen the solvent is evaporated
  4. customthe residue is sequentially triturated
  5. filtrationfiltrated with ethyl acetate and with a minimum of cold water
  6. customPurification of the residue by flash chromatography (SiO2, heptane/ethyl acetate 1:2)

Sources & evidence

ORD record
ord-06a5f9283694411d8b7c1cc70a110ade
Source dataset
uspto-grants-2014_02
Patent number
US08658801B2

Reaction notes

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