N-butyl-4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine → N-butyl-4-[2-(4-fluorophenyl)-7-methylpyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine

HRID 1797080Notes

Reaction equation

HRID 1797080 reaction equation
[CH2:1]([NH:5][C:6]1[N:11]=[C:10]([C:12]2[C:13]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[N:14][N:15]3[C:20](Cl)=[CH:19][CH:18]=[CH:17][C:16]=23)[CH:9]=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].[CH3:29][Zn]C>O1CCCC1>[CH2:1]([NH:5][C:6]1[N:11]=[C:10]([C:12]2[C:13]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)=[N:14][N:15]3[C:20]([CH3:29])=[CH:19][CH:18]=[CH:17][C:16]=23)[CH:9]=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 22174847N-butyl-4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamineHCID 178477796HCID 178477796, compound

Product 1

HCID 10292858N-butyl-4-[2-(4-fluorophenyl)-7-methylpyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamineYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-butyl-4-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine (80 mg, 0.20 mmol) in tetrahydrofuran (1 mL) was added dimethylzinc (304 μL, 2.0 M in toluene, 0.60 mmol) and tetrakis(triphenyl-phosphine)palladium(0) (23 mg, 0.02 mmol). The reaction mixture was heated at 60° C. for 16 hours. The reaction mixture was cooled, then quenched with ice water. The resultant mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. Filtration and concentration, followed by flash chromatography (3:1 hexanes:ethyl acetate) provided N-butyl-4-[2-(4-fluorophenyl)-7-methylpyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinamine (24 mg, 32%) as a yellow solid. Rf 0.33 (2:1 hexanes:ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.32 (d, 1H), 8.04 (d, 1H), 7.64 (m, 2H), 7.27 (m, 1H), 7.13 (t, 2H), 6.77 (d, 1H), 6.31 (d, 1H), 5.17 (br, 1H), 3.48 (m, 2H), 2.80 (s, 3H), 1.65 (m, 2H), 1.45 (m, 2H), 0.97 (t, 3H); MS m/z 376 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customquenched with ice water
  3. extractionThe resultant mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-9a75ff2a14ac4adb825a4e0f0372cd23
Source dataset
uspto-grants-2006_04
Patent number
US07034030B2

Reaction notes

Loading…