反応 #88446

反応方程式

3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

Compound 49

3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

Cs2CO3

2-(dimethylamino)acetic acid

3-chlorophenol

→

3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenoxy)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

収率 63.0%

溶媒

dioxane

反応条件

後処理

1. 1
   温度The reaction was heated at 140° C. (MW) for 2.5 h
2. 2
   ろ過filtered through a pad of Celite
3. 3
   workup.ADDITIONThe filtrate was diluted with EA (20 mL) and water (20 mL)
4. 4
   乾燥The organic layer was dried over Na2SO4
5. 5
   濃縮concentrated to a residue which
6. 6
   その他was purified by chromatography
7. 7
   洗浄eluted with PE/EA (2:1)

実験手順

To a mixture of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (See Compound 49, step 3, 383 mg, 1 mmol) CuI (24.7 mg, 0.13 mmol), Cs2CO3 (650 mg, 2 mmol), 2-(dimethylamino)acetic acid (51.5 mg, 0.5 mmol) in dioxane (6 mL) was added 3-chlorophenol (192 mg, 1.5 mmol). The reaction was heated at 140° C. (MW) for 2.5 h, cooled to RT and filtered through a pad of Celite. The filtrate was diluted with EA (20 mL) and water (20 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenoxy)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (300 mg, 63% yield) as a solid. LCMS: MH+ 476 and TR=2.377 min.

出典