تفاعل #6049

معادلة التفاعل

DBU

Adenine

methyl 1-cyclobutene carboxylate

DBU

→

title compound

المردود 61.0%

9-(2-methoxycarbonyl-1-cyclobutyl)adenine

المردود 61.0%

المذيبات

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGstirring
2. 2
   أخرىAfter a total of 136 h, the reaction was quenched by the addition of 0.28 mL of glacial acetic acid
3. 3
   تركيزconcentrated in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in approximately 3 mL of methylene chloride
5. 5
   أخرىpurified on a 1.5×45 cm silica gel column
6. 6
   غسيلeluted @ 5-10 psi with a step-wise solvent gradient of methanol in methylene chloride
7. 7
   درجة الحرارةincreasing in 2% steps to 8% methanol

الإجراء التجريبي

Adenine (486 mg, 3.6 mmol) was combined with an excess of methyl 1-cyclobutene carboxylate (~25 mmol) from Step B of Example 35 and 53 μL (0.36 mmol) of DBU in 75 mL of acetonitrile and the mixture was stirred at ambient temperature, under a nitrogen atmosphere. After 66 h, a second 53 μL aliquot of DBU was added and stirring continued. After a total of 136 h, the reaction was quenched by the addition of 0.28 mL of glacial acetic acid and concentrated in vacuo. The residue was dissolved in approximately 3 mL of methylene chloride and purified on a 1.5×45 cm silica gel column eluted @ 5-10 psi with a step-wise solvent gradient of methanol in methylene chloride, starting with 100% methylene chloride and increasing in 2% steps to 8% methanol, each step was 200 mL of solvent. The title compound was obtained in 61% yield (542mg) as a mixture of cis and trans isomers and equilibrated to the desired trans isomer by treating the mixture of isomers with 394 μL of DBU in 35 mL of acetonitrile at 45° C., under nitrogen, for 46 h. The reaction mixture was concentrated in vacuo and the residue was dissolved in approximately 2 mL of methylene chloride and purified on a 1.5×45 cm silica gel column eluted @5 psi with a step-wise solvent gradient of 200 mL of methylene chloride followed by 200 mL of 5% methanol in methylene chloride and 200 mL of 7% methanol in methylene chloride to give 502 mg (57% yield) of the desired trans isomer of the title compound; 1H NMR (CD3OD) δ 2.11 (m, 1H), 2.30 (m, 1H), 2.45 (m, 1H), 2.77 (m, 1H), 3.68 (s, 3H), 4.01 (m, 1H), 5.18 (q, 1H), 8.20 (s, 1H), 8.25 (s, 1H); MS DCI-NH3M/Z: 248 (M+H)+.

المصدر