Water → 2-[6-[2-(4-Cyano-phenyl)-2H-pyrazol-3-yl]-7-methyl-3-oxo-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-2-yl]-N,N-dimethyl-acetamide

HRID 1497769Notes

Reaction equation

HRID 1497769 reaction equation
[CH3:1][C:2]1[C:7]([C:8]2[N:12]([C:13]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][CH:14]=3)[N:11]=[CH:10][CH:9]=2)=[CH:6][N:5]2[C:21](=[O:24])[NH:22][N:23]=[C:4]2[C:3]=1[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:42][C:43]([N:45]([CH3:47])[CH3:46])=[O:44].O>CN(C=O)C>[C:17]([C:16]1[CH:19]=[CH:20][C:13]([N:12]2[C:8]([C:7]3[C:2]([CH3:1])=[C:3]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:32])[F:33])[CH:26]=4)[C:4]4[N:5]([C:21](=[O:24])[N:22]([CH2:42][C:43]([N:45]([CH3:47])[CH3:46])=[O:44])[N:23]=4)[CH:6]=3)=[CH:9][CH:10]=[N:11]2)=[CH:14][CH:15]=1)#[N:18]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 730512754-{5-[7-Methyl-3-oxo-8-(3-trifluoromethyl-phenyl)-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridin-6-yl]-pyrazol-1-yl}-benzonitrile

Product 1

HCID 730512772-[6-[2-(4-Cyano-phenyl)-2H-pyrazol-3-yl]-7-methyl-3-oxo-8-(3-trifluoromethyl-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-2-yl]-N,N-dimethyl-acetamideYield 33.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-{5-[7-methyl-3-oxo-8-(3-trifluoromethyl-phenyl)-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridin-6-yl]-pyrazol-1-yl}-benzonitrile (Ex. 9, 55 mg. 0.12 mmol) in DMF (3 mL) was added cesium carbonate (58 mg, 0.18 mmol) followed by 2-chloro-N,N-dimethylacetamide (19 μL, 0.18 mmol). The reaction mixture was stirred at RT for 18 hrs then water was added and the reaction mixture was extracted with EtOAc (2×20 mL). The combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by preparative HPLC, eluting with a gradient of 20-70% MeCN in water (+0.1% formic acid) to give the title compound as a yellow solid (22 mg).

Workup

  1. extractionthe reaction mixture was extracted with EtOAc (2×20 mL)
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe resultant residue was purified by preparative HPLC
  6. washeluting with a gradient of 20-70% MeCN in water (+0.1% formic acid)

Sources & evidence

ORD record
ord-33a1f3c3ce0a4a14acaccf7c13fe97a8
Source dataset
uspto-grants-2015_12
Patent number
US09199984B2

Reaction notes

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