تفاعل #92178

معادلة التفاعل

6-bromo-1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-1,2, 3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde

6-bromo-1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde

Compound 2

6-bromo-1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde

3-(trifluoromethoxy)phenol

K2CO3

→

1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy) phenoxy)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde

المردود 40.8%

المذيبات

DMSO

water

EA

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooled to RT
2. 2
   غسيلThe organic layer was washed with aq. 1N LiCl (3×5 mL)
3. 3
   تجفيفdried over Na2SO4
4. 4
   تركيزconcentrated to a residue which
5. 5
   أخرىwas purified by chromatography
6. 6
   غسيلeluted with PE/EA (5:1 to 3:1)

الإجراء التجريبي

To a solution of 6-bromo-1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-1,2, 3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde (See Compound 2, Step 4, 100 mg, 0.232 mmol) in DMSO (2 mL) was added 3-(trifluoromethoxy)phenol (82.6 mg, 0.464 mmol) and K2CO3 (96.1 mg, 0.696 mmol). The reaction was heated to 80° C. for 18 h, cooled to RT then diluted with EA (10 mL) and water (10 mL). The organic layer was washed with aq. 1N LiCl (3×5 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (5:1 to 3:1) to give 1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy) phenoxy)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde (50 mg, 40.8% yield) as a solid. LCMS: [MH+-THP] 445 and TR=1.834 min.

المصدر