Diethyl Ether → 2-(4-Fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine

HRID 1796531Notes

Reaction equation

HRID 1796531 reaction equation
CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:8]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)=[N:9][N:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=12)=O.S(O)(O)(=O)=O.[N:33]1([C:38](=[NH:40])[NH2:39])[CH2:37][CH2:36][CH2:35][CH2:34]1.C(=O)([O-])[O-].[K+].[K+].CCOCC>CN1CCCC1=O.O>[F:26][C:23]1[CH:22]=[CH:21][C:20]([C:8]2[C:7]([C:5]3[CH:4]=[CH:3][N:39]=[C:38]([N:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)[N:40]=3)=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:17])([F:19])[F:18])=[CH:15][N:10]3[N:9]=2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 11501715(2E)-3-(dimethylamino)-1-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-propen-1-oneHCID 13221242Pyrrolidine-1-carboximidamide, sulfuric acid

Product 1

HCID 221809222-(4-Fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridineYield 71%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of (2E)-3-(dimethylamino)-1-[2-(4-fluorophenyl)-6-(trifluoromethyl)-pyrazolo[1,5-a]pyridin-3-yl]-2-propen-1-one (100 mg, 0.27 mmol) in 1-methyl-2-pyrrolidinone (3 mL) was added 1-pyrrolidinecarboximidamide sulfate (111 mg, 0.53 mmol), and potassium carbonate (73 mg, 0.53 mmol). The mixture was heated at reflux for 8 hours. Upon cooling to room temperature, ether was added followed by water. The organics were washed with brine, and the aqueous layer was extracted with ether. The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica (6:1 hexanes-ethyl acetate) to give 2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine (80 mg, 71%) as a foam. 1H NMR (CDCl3): δ 8.86 (s, 1 H), 8.61 (d, 1 H), 8.19 (m, 1 H), 7.67 (m, 2 H), 7.46 (d, 1 H), 7.19 (m, 2 H), 6.31 (m, 1 H), 3.70 (m, 4 H), 2.08 (m, 4 H); 19F NMR (CDCl3) δ −62.68, −112.27.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 8 hours
  3. washThe organics were washed with brine
  4. extractionthe aqueous layer was extracted with ether
  5. dry with materialThe combined organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica (6:1 hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-08585f9499914b67a5794df0c481ed58
Source dataset
uspto-grants-2006_04
Patent number
US07030134B2

Reaction notes

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