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

HRID 1752625Notes

Reaction equation

HRID 1752625 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:68]([CH3:69])[C:67]4[CH:70]=[CH:71][CH:72]=[CH:73][C:66]=4[N:65]=3)[C:60](=[O:61])[C:51]=12.[NH:74]1[CH2:79][CH2:78][O:77][CH2:76][CH2:75]1>O1CCOCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH3:57][N:54]1[C:55](=[O:56])[C:50]([N:74]2[CH2:79][CH2:78][O:77][CH2:76][CH2:75]2)=[C:51]2[C:60](=[O:61])[N:59]([CH2:62][CH2:63][C:64]3[N:68]([CH3:69])[C:67]4[CH:70]=[CH:71][CH:72]=[CH:73][C:66]=4[N:65]=3)[CH2:58][C:52]2=[CH:53]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 717435967-Chloro-5-methyl-2-(2-(1-methyl-1H-benzo[D]imidazol-2-YL)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-C]pyridine-1,6(5H)-dione

Product 1

HCID 862960645-Methyl-2-[2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-7-morpholin-4-yl-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dioneYield 8.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Palladium diacetate (189 mg, 0.841 mmol), Xantphos (486 mg, 0.841 mmol) and Cs2CO3 (822 mg, 2.52 mmol) were each rapidly added in sequence to a suspension of 7-chloro-5-methyl-2-[2-(1-methyl-1H-benzoimidazol-2-yl)-ethyl]-3,5-dihydro-2H-pyrrolo[3,4-c]pyridine-1,6-dione (300 mg, 0.841 mmol, see Example c8)) and morpholine (220 mg, 2.52 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 (30 mg, 0.074 mmol, 8.76% yield)

Workup

  1. customThe solvent was removed
  2. 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-b2ee1e073a054567bf55774cc7c20fae
Source dataset
uspto-grants-2015_10
Patent number
US09163019B2

Reaction notes

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