反応 #643786

反応方程式

product

8-(2,6-difluoro-phenyl)-4-(4-fluoro-2-methyl-phenyl)-2-methane-sulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one

NaH

2-(hydroxymethyl)-1,3-propanediol

→

crude product

8-(2,6-Difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(3-hydroxy-2-hydroxymethylpropoxy)-8H-pyrido[2,3-d]pyrimidin-7-one

溶媒

THF

THF

反応条件

後処理

1. 1
   温度was then cooled to −78°
2. 2
   温度to warm to 23°
3. 3
   workup.STIRRINGstir for 2 h
4. 4
   その他The solvents were removed in vacuo
5. 5
   その他the residue was partitioned between EtOAc and H2O
6. 6
   洗浄The organic phase was washed with H2O
7. 7
   乾燥dried over anhyd Na2SO4
8. 8
   ろ過filtered
9. 9
   その他evaporated

実験手順

NaH (15 mg, 0.6 mmol) was added to 2-(hydroxymethyl)-1,3-propanediol in THF (5 mL). The mixture was allowed to stir at 23° under Ar for 10 min and was then cooled to −78°. The product of Example 48 (224 mg, 0.5 mmol) in THF (5 mL) was added at −78° and the mixture allowed to warm to 23° and stir for 2 h. The solvents were removed in vacuo, and the residue was partitioned between EtOAc and H2O. The organic phase was washed with H2O, satd aq NaCl, dried over anhyd Na2SO4, filtered and evaporated to give the crude product. Flash chromatography eluted with 70% EtOAc/CH2Cl2 the title compound as a white-amorphous solid. mp 77-81°, LC MS m/z=472 (MH+) Retention time=1.79 min.

出典