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

HRID 1752627Notes

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:65]=[C:66]4[CH:71]=[CH:70][CH:69]=[CH:68][N:67]4[CH:72]=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]>[N:65]1[C:64]([CH2:63][CH2:62][N:59]2[C:60](=[O:61])[C:51]3[C:52](=[CH:53][N:54]([CH3:57])[C:55](=[O:56])[C:50]=3[N:73]3[CH2:78][CH2:77][O:76][CH2:75][CH2:74]3)[CH2:58]2)=[CH:72][N:67]2[CH:68]=[CH:69][CH:70]=[CH:71][C:66]=12

Participants

Conditions

Temperature: 120 °C

Procedure

Palladium diacetate (65.5 mg, 0.292 mmol), Xantphos (169 mg, 0.292 mmol) and Cs2CO3 (285 mg, 0.875 mmol) were each rapidly added in sequence to a suspension of 7-chloro-2-(2-imidazo[1,2-a]pyridin-2-yl-ethyl)-5-methyl-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione (100 mg, 0.292 mmol, see Example c5)) and morpholine (76 mg, 0.875 mmol) in dioxane (1 ml). The reaction 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: 10:90 to 35:65 over 15 min), column: Boston Analytics, C-18, 10 μm, 21×250 mm) to afford the title compound (24.1 mg, 0.061 mmol, 21.00% yield).

Workup

customThe solvent was removed
customthe resulting mixture was purified by preparative HPLC (system: Waters 2767 PHW003, eluent: MeCN/ammonium acetate buffer (gradient: 10:90 to 35:65 over 15 min), column: Boston Analytics, C-18, 10 μm, 21×250 mm)

Sources & evidence

ORD record: ord-07912f559abe4a7699df6b52d1b030b2
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163019B2

Reaction notes

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