N-methyl-2-pyrrolidone → 4-(2,5-dimethylpyrimidin-4-yl)-N-(6-fluoro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1-methyl-1H-pyrazole-5-carboxamide

HRID 874420Notes

Reaction equation

HRID 874420 reaction equation
CN1CCCC1=O.[CH3:8][C:9]1[N:14]=[C:13]([C:15]2[CH:16]=[N:17][N:18]([CH3:23])[C:19]=2[C:20]([OH:22])=O)[C:12]([CH3:24])=[CH:11][N:10]=1.Cl.[F:26][C:27]1[C:28]([NH2:42])=[CH:29][C:30]2[N:31]([N:33]=[C:34]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[N:35]=2)[CH:32]=1.C(N(C(C)C)CC)(C)C>O>[CH3:8][C:9]1[N:14]=[C:13]([C:15]2[CH:16]=[N:17][N:18]([CH3:23])[C:19]=2[C:20]([NH:42][C:28]2[C:27]([F:26])=[CH:32][N:31]3[N:33]=[C:34]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[N:35]=[C:30]3[CH:29]=2)=[O:22])[C:12]([CH3:24])=[CH:11][N:10]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 903834284-(2,5-dimethylpyrimidin-4-yl)-1-methyl-1H-pyrazole-5-carboxylic acidHCID 1177765626-Fluoro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-amine hydrochloride

Product 1

HCID 903833524-(2,5-dimethylpyrimidin-4-yl)-N-(6-fluoro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1-methyl-1H-pyrazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

An N-methylpyrrolidone (7.7 ml) solution of the 4-(2,5-dimethylpyrimidin-4-yl)-1-methyl-1H-pyrazole-5-carboxylic acid (715 mg) obtained in (Example 3.22) <Step 2>, 6-fluoro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-amine hydrochloride (obtained according to the method described in International Publication No. WO2012/076430, p. 80, Example 30-h) (815 mg), 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate methanaminium (2.34 g), and diisopropylethylamine (2.69 ml) was stirred at 80° C. for 3 hours. Thereafter, water was added to the reaction solution, and the mixed solution was then extracted with ethyl acetate. Organic layers were combined, and the combined organic layer was then dried over anhydrous sodium sulfate. Subsequently, the solvent was distilled away under reduced pressure, and the obtained residue was then purified by silica gel column chromatography (NH silica gel: eluent; heptane:ethyl acetate=3:1-1:1). The obtained fraction was concentrated under reduced pressure. The obtained residue (solid) was triturated with methanol to obtain the title compound (377 mg) in the form of a colorless solid.

Workup

  1. customobtained
  2. extractionthe mixed solution was then extracted with ethyl acetate
  3. dry with materialthe combined organic layer was then dried over anhydrous sodium sulfate
  4. distillationSubsequently, the solvent was distilled away under reduced pressure
  5. customthe obtained residue was then purified by silica gel column chromatography (NH silica gel: eluent; heptane:ethyl acetate=3:1-1:1)
  6. concentrationThe obtained fraction was concentrated under reduced pressure
  7. customThe obtained residue (solid) was triturated with methanol

Sources & evidence

ORD record
ord-69d9bf21218c44f69f06710420c29404
Source dataset
uspto-grants-2015_03
Patent number
US08980889B2

Reaction notes

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