Diethyl ((6-methoxypyridin-2-yl)methyl)phosphonate → (E)-tert-butyl 4-(2-(2-(6-methoxypyridin-2-yl)vinyl)-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)benzoate

HRID 1772711Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1772711
[CH3:1][O:2][C:3]1[N:8]=[C:7]([CH2:9]P(=O)(OCC)OCC)[CH:6]=[CH:5][CH:4]=1.[Li]CCCC.[CH:23]([C:25]1[N:26]=[C:27]2[C:32]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[N:31][CH:30]=[C:29]([C:39]3[CH:51]=[CH:50][C:42]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[CH:41][CH:40]=3)[N:28]2[CH:52]=1)=O>C1COCC1>[CH3:1][O:2][C:3]1[N:8]=[C:7](/[CH:9]=[CH:23]/[C:25]2[N:26]=[C:27]3[C:32]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)=[N:31][CH:30]=[C:29]([C:39]4[CH:51]=[CH:50][C:42]([C:43]([O:45][C:46]([CH3:49])([CH3:47])[CH3:48])=[O:44])=[CH:41][CH:40]=4)[N:28]3[CH:52]=2)[CH:6]=[CH:5][CH:4]=1

Komponenten

5

Edukt 3

HCID 86076821Diethyl ((6-methoxypyridin-2-yl)methyl)phosphonateHCID 117733763tert-Butyl 4-(2-formyl-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)benzoateHCID 178418339Butyllithium

Produkt 1

HCID 117728123(E)-tert-butyl 4-(2-(2-(6-methoxypyridin-2-yl)vinyl)-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)benzoate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of diethyl ((6-methoxypyridin-2-yl)methyl)phosphonate (76.2 mg, 0.29 mmol, prepared according to literature procedure: J. Med. Chem. 2005, 48, 5884-5887), n-BuLi (0.184 mL, 0.29 mmol, 1.6 M in hexanes) was added dropwise. After stirring the resulting mixture for 15 min at rt, it was slowly added to a suspension of compound 67a (100 mg, 0.25 mmol) in THF (5 mL). The resulting mixture was stirred at rt for 30 min and quenched with saturated NH4Cl (2 mL). The reaction mixture was treated with water (20 mL) and extracted with EtOAc (2×40 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue obtained was purified by flash column chromatography on silica gel (0-100% EtOAc/heptanes) to give (E)-tert-butyl 4-(2-(2-(6-methoxypyridin-2-yl)vinyl)-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)benzoate, which was subjected to TFA deprotection using the methods described in Example 57, Step A to yield the title compound 7 containing 0.1 eq. of TFA. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 8.25 (s, 1H), 8.11 (m, J=7.8 Hz, 2H), 7.83 (m, J=7.8 Hz, 2H), 7.63-7.69 (m, 1H), 7.69-7.75 (m, 1H), 7.49 (s, 1H), 7.40 (d, J=15.7 Hz, 1H), 7.08 (d, J=7.1 Hz, 1H), 6.70 (d, J=8.1 Hz, 1H), 4.29 (br. s., 4H), 3.92 (s, 3H), 3.80 (br. s., 4H). Mass Spectrum (LCMS, ESI pos.) Calcd. for C25H23N5O4: 458.2 [M+H]. found 458.4.

Aufarbeitung

  1. stirringThe resulting mixture was stirred at rt for 30 min
  2. customquenched with saturated NH4Cl (2 mL)
  3. additionThe reaction mixture was treated with water (20 mL)
  4. extractionextracted with EtOAc (2×40 mL)
  5. washThe combined organic layers were washed with brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue obtained
  10. customwas purified by flash column chromatography on silica gel (0-100% EtOAc/heptanes)

Quellen und Nachweise

ORD-Eintrag
ord-3b441df2af3d4082844f7d51ea1c307f
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09249163B2

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