HCID 10400931, compound → HCID 10315728, compound

HRID 859976Notes

Reaction equation

HRID 859976 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9]2[C:10]([CH:18]=[O:19])=[N:11][N:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=23)[CH:6]=[CH:5][N:4]=1.[C:20]1([Mg]Br)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O1CCCC1>[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9]2[C:10]([CH:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[OH:19])=[N:11][N:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=23)[CH:6]=[CH:5][N:4]=1

Participants

4

Reactant 2

HCID 10400931HCID 10400931, compoundHCID 178418255HCID 178418255, compound2×

Product 1

HCID 10315728HCID 10315728, compoundYield 82.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cold (−78° C.) solution of 3-[2-(methylthio)pyrimidin-4-yl]pyrazolo[1,5-a]pyridine-2-carbaldehyde (520 mg, 1.92 mmol) in tetrahydrofuran (40 mL) was added phenylmagnesium bromide (2.88 mL 1.0 M in tetrahydrofuran, 2.88 mmol). The reaction was warmed to 0° C. and stirred for 1 hour. The reaction mixture was then recooled to −78° C. and additional phenylmagnesium bromide (2.00 mL, 1.0 M in tetrahydrofuran, 2.00 mmol) was added and stirred at room temperature for 14 hours. The reaction was quenched with water and the resulting mixture was concentrated in vacuo to remove the excess tetrahydrofuran. The resulting aqueous mixture was extracted with dichloromethane. The organic layer was washed with water and dried over magnesium sulfate. Filtration and concentration, followed by flash chromatography (49:1 dichloromethane:methanol) provided {3-[2-(methylthio)pyrimidin-4-yl]pyrazolo[1,5-a]pyridin-2-yl}(phenyl)methanol (550 mg, 82%) as a white solid. Rf 0.31 (49:1 dichloromethane:methanol); 1H NMR (CDCl3) δ 8.52 (d, 1H), 8.40 (d, 1H), 7.87 (d, 1H), 7.43–7.13 (m, 7H), 6.93 (t, 1H), 6.21 (s, 1H), 2.60 (s, 3H); MS m/349 (M+1).

Workup

  1. customwas then recooled to −78° C.
  2. stirringstirred at room temperature for 14 hours
  3. customThe reaction was quenched with water
  4. concentrationthe resulting mixture was concentrated in vacuo
  5. customto remove the excess tetrahydrofuran
  6. extractionThe resulting aqueous mixture was extracted with dichloromethane
  7. washThe organic layer was washed with water
  8. dry with materialdried over magnesium sulfate
  9. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-1df2e13b999e41449e3d595a55c79afa
Source dataset
uspto-grants-2006_12
Patent number
US07153863B2

Reaction notes

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