Реакция #1755488

Уравнение реакции

(R)-6-(4-chlorophenyl)-3-(4-(2-cyclopropyl-2-hydroxyethoxy)-3-methoxyphenyl)-thieno[3,2-d]pyrimidin-4(3H)-one

diisopropylcarbodiimide

N-(t-butoxycarbonyl)-L-valine

→

title compound

(S)—((R)-2-(4-(6-(4-Chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-1-cyclopropylethyl) 2-amino-3-methylbutanoate

Растворители

CH2Cl2

CH2Cl2

Условия реакции

Обработка

1. 1
   Промывкаwashed with aq NaHCO3
2. 2
   ЭкстракцияAfter extracting the aqueous layer with CH2Cl2
3. 3
   Промывкаthe combined organic layers were washed sequentially with water and brine
4. 4
   Сушкаdried over Na2SO4
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеthe filtrate concentrated under reduced pressure
7. 7
   ДругоеThe residue was purified by flash chromatography (silica gel, EtOAC/hexane 0 to 40% gradient)

Методика

A mixture of (R)-6-(4-chlorophenyl)-3-(4-(2-cyclopropyl-2-hydroxyethoxy)-3-methoxyphenyl)-thieno[3,2-d]pyrimidin-4(3H)-one described in Example 1 (1.3 g, 2.33 mmol), diisopropylcarbodiimide (0.88 g, 6.99 mmol), 4-dimethylaminopyridine (142 mg, 1.16 mmol) and N-(t-butoxycarbonyl)-L-valine (1.52 g, 6.99 mmol) in CH2Cl2 (10 mL) was stirred at rt for 19 h. By LCMS analysis no starting alcohol remained. The suspension was diluted with CH2Cl2 and washed with aq NaHCO3. After extracting the aqueous layer with CH2Cl2, the combined organic layers were washed sequentially with water and brine, dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, EtOAC/hexane 0 to 40% gradient) to afford the title compound (1.12 g) as a white solid. 1H NMR (CDCl3) δ 0.41-0.46 (m, 1H), 0.49-0.53 (m, 1H), 0.58-0.63 (m, 1H), 0.64-0.68 (m, 1H), 0.925 (d, J=7 Hz), 3H), 0.99 (d, J=7 Hz), 1.16-1.19 (m, 1H), 1.44 (s, 9H), 2.19-2.23 (m, 1H), 3.86 (s, 3H), 4.23-4.32 (m, 3H), 4.67-4.71 (m, 1H), 5.06 (d, J=2 Hz, 1H), 6.92-6.95 (m, 2H), 7.04 (d, J=2 Hz, 1H), 7.26 (s, 2H), 7.45 (d, J=2 Hz), 7.54 (s, 1H), 7.66 (d, J=2 Hz, 2H), 8.16 (s, 1H). LCMS (ES): m/z 669 [M+H].

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