반응 #1755488

반응 방정식

(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

용매

CH2Cl2

CH2Cl2

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후처리

1. 1
   세척washed with aq NaHCO3
2. 2
   추출After extracting the aqueous layer with CH2Cl2
3. 3
   세척the combined organic layers were washed sequentially with water and brine
4. 4
   건조dried over Na2SO4
5. 5
   여과filtered
6. 6
   농축the filtrate concentrated under reduced pressure
7. 7
   기타The residue was purified by flash chromatography (silica gel, EtOAC/hexane 0 to 40% gradient)

실험 절차

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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