Carbon Tetrachloride → 7-Chloro-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine

HRID 1062853Notes

Reaction equation

HRID 1062853 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[N:22]=3)=[C:11]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.C([Li])CCC.C(Cl)(Cl)(Cl)[Cl:38]>O1CCCC1>[Cl:38][C:15]1[N:10]2[N:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:20]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([N:27]4[CH2:28][CH2:29][CH2:30][CH2:31]4)[N:22]=3)=[C:11]2[CH:12]=[CH:13][C:14]=1[C:16]([F:19])([F:17])[F:18]

Participants

5

Reactant 3

HCID 5943Carbon TetrachlorideHCID 221809222-(4-Fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridineHCID 178418339Butyllithium

Product 1

HCID 221809127-Chloro-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridineYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cold (−78° C.) solution of 2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine (86 mg, 0.20 mmol) in tetrahydrofuran (5 mL) was added n-butyllithium (0.30 mL, 1.6 M in hexane, 0.48 mmol) dropwise. The dark solution was stirred for 3 minutes, and then carbon tetrachloride (1 mL) was added. After 15 minutes, the bath was removed and the solution allowed to warm to room temperature and stirred an additional 15 minutes. Water was added then ether. 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 (4:1 hexanes-ethyl acetate) to give 7-chloro-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine (55 mg, 59%) as a solid. 1H NMR (CDCl3): δ 8.50 (d, 1 H), 8.11 (d, 1 H), 7.62 (dd, 2 H), 7.50 (d, 1 H), 7.11 (t, 2 H), 6.22 (d, 1 H), 3.62 (m, 4 H), 2.01 (m, 4 H); MS m/z 462 (M+1).

Workup

  1. waitAfter 15 minutes
  2. customthe bath was removed
  3. stirringstirred an additional 15 minutes
  4. additionWater was added
  5. washThe organics were washed with brine
  6. extractionthe aqueous layer was extracted with ether
  7. dry with materialThe combined organics were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography on silica (4:1 hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-ed279c8e553244009ac6b679d6311ccf
Source dataset
uspto-grants-2005_11
Patent number
US06962914B2

Reaction notes

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