반응 #2073584

반응 방정식

HCl

4-{[2-(4-morpholinyl)ethyl]oxy}benzoic acid

product

4-{6-[(3-Aminophenyl)oxy]-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl}-furazan-3-amine

oxalylchloride

→

solid

수율 83.0%

N-(3-{[2-(4-amino-furazan-3-yl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]oxy}phenyl)-4-{[2-(4-morpholinyl)ethyl]oxy}benzamide

수율 83.0%

용매

CH2Cl2

DMF

pyridine

반응 조건

후처리

1. 1
   온도This mixture was then heated
2. 2
   온도to reflux until a clear solution
3. 3
   기타resulted
4. 4
   농축The reaction mixture was then concentrated
5. 5
   workup.ADDITIONadded CH2Cl2 (20 mL)
6. 6
   workup.ADDITIONA suspension of the above product in CH2Cl2 (100 mL)
7. 7
   workup.DISTILLATIONthe CH2Cl2 was distilled off
8. 8
   workup.ADDITIONCH2Cl2 (200 mL) was added to the cooled reaction mixture
9. 9
   workup.STIRRINGstirred for 15 min
10. 10
    여과filtered
11. 11
    기타to provide a first crop of product (crop 1)
12. 12
    농축The filtrate was concentrated in vacuo
13. 13
    세척washed with water (4×), brine
14. 14
    건조dried over Na2SO4
15. 15
    여과filtered
16. 16
    농축concentrated
17. 17
    기타to provide Crop 2
18. 18
    기타recrystallized from MeOH

실험 절차

Under argon, to a suspension of the HCl salt of 4-{[2-(4-morpholinyl)ethyl]oxy}benzoic acid (3.98 g, 13.8 mmol) in CH2Cl2 (100 ml) was added DMF (40 μl), followed with oxalylchloride (3.6 ml, 41.4 mmol). This mixture was then heated to reflux until a clear solution resulted. The reaction mixture was then concentrated, added CH2Cl2 (20 mL) and reconcentrated. A suspension of the above product in CH2Cl2 (100 mL), was added to a suspension of the product of Example 3 (3.96 g, 11.7 mmol) in pyridine (30 mL). This mixture was then heated to 70° C., the CH2Cl2 was distilled off, then stirred for 1 h. CH2Cl2 (200 mL) was added to the cooled reaction mixture, stirred for 15 min and then filtered to provide a first crop of product (crop 1). The filtrate was concentrated in vacuo and the residue taken up in EtOAc, washed with water (4×), brine, dried over Na2SO4, filtered and concentrated to provide Crop 2. Crops 1 and 2 were combined and recrystallized from MeOH to afforded a off white solid (5.54 g, 83%). 1H NMR (400 MHz, DMSO) δ ppm 11.35 (bs, 1H), 10.22 (s, 1H), 8.79 (d, 1H, 0.8 Hz), 7.99 (d, 2H, 8.8 Hz), 7.58-7.64 (m, 3H), 7.37 (t, 1H, 8.0 Hz), 7.12 (d, 2H, 8.8 Hz), 6.95 (s, 2H), 6.84-6.87 (m, 1H), 4.70 (q, 2H, 7.2 Hz), 4.53 (bs, 2H), 3.81-3.98 (m, 4H), 3.49-3.58 (m, 4H), 3.18-3.36 (m, 2H), 1.41 (t, 3H, 7.2 Hz). MS (ES+) m/e 571 [M+H]+.

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