Morpholine → 5-Methyl-7-morpholin-4-yl-2-(2-[1,2,4]triazolo[1,5-a]pyridin-2-yl-ethyl)-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione

HRID 1752629Notes

Reaction equation

CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:50]1[C:55](=[O:56])[N:54]([CH3:57])[CH:53]=[C:52]2[CH2:58][N:59]([CH2:62][CH2:63][C:64]3[N:72]=[C:67]4[CH:68]=[CH:69][CH:70]=[CH:71][N:66]4[N:65]=3)[C:60](=[O:61])[C:51]=12.[NH:73]1[CH2:78][CH2:77][O:76][CH2:75][CH2:74]1>O1CCOCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH3:57][N:54]1[C:55](=[O:56])[C:50]([N:73]2[CH2:78][CH2:77][O:76][CH2:75][CH2:74]2)=[C:51]2[C:60](=[O:61])[N:59]([CH2:62][CH2:63][C:64]3[N:72]=[C:67]4[CH:68]=[CH:69][CH:70]=[CH:71][N:66]4[N:65]=3)[CH2:58][C:52]2=[CH:53]1

Participants

Conditions

Temperature: 120 °C

Procedure

Palladium diacetate (65.3 mg, 0.291 mmol), Xantphos (168 mg, 0.291 mmol) and Cs2CO3 (284 mg, 0.873 mmol) were each rapidly added in sequence to a suspension of 7-chloro-5-methyl-2-(2-[1,2,4]triazolo[1,5-a]pyridin-2-yl-ethyl)-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione (100 mg, 0.291 mmol, see Example c6)) and morpholine (25.3 mg, 0.291 mmol) in dioxane (5 ml). The reaction mixture was heated in a microwave at about 120° C. for about 40 min. The solvent was removed and the resulting mixture was purified by preparative HPLC (system: Waters 2767 PHW003, eluent: MeCN/ammonium acetate buffer (gradient: 7:93 to 30:70 over 15 min), column: Boston Analytics, C-18, 10 μm, 10×250 mm) to afford the title compound (17 mg, 0.043 mmol, 14.82% yield).

Workup

customThe solvent was removed
customthe resulting mixture was purified by preparative HPLC (system: Waters 2767 PHW003, eluent: MeCN/ammonium acetate buffer (gradient: 7:93 to 30:70 over 15 min), column: Boston Analytics, C-18, 10 μm, 10×250 mm)

Sources & evidence

ORD record: ord-2f7af32a9a084663bf0985f7d0dc1e35
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163019B2

Reaction notes

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