Water → 1-methyl-3-morpholino-4-(4-(quinolin-2-ylmethoxy)phenyl)-1H-pyrrole-2,5-dione

HRID 655412Notes

Reaction equation

HRID 655412 reaction equation
Br[C:2]1[C:3](=[O:15])[N:4]([CH3:14])[C:5](=[O:13])[C:6]=1[N:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.C([O-])([O-])=O.[Cs+].[Cs+].O.CC1(C)C(C)(C)OB([C:31]2[CH:48]=[CH:47][C:34]([O:35][CH2:36][C:37]3[CH:46]=[CH:45][C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[N:38]=3)=[CH:33][CH:32]=2)O1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:14][N:4]1[C:3](=[O:15])[C:2]([C:31]2[CH:32]=[CH:33][C:34]([O:35][CH2:36][C:37]3[CH:46]=[CH:45][C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[N:38]=3)=[CH:47][CH:48]=2)=[C:6]([N:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)[C:5]1=[O:13]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 593547463-bromo-1-methyl-4-morpholino-1H-pyrrole-2,5-dione

Product 1

HCID 593548311-methyl-3-morpholino-4-(4-(quinolin-2-ylmethoxy)phenyl)-1H-pyrrole-2,5-dioneYield 45%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 3-bromo-1-methyl-4-morpholino-1H-pyrrole-2,5-dione (100 mg, 0.36 mol) in DMF (40 mL) were added Cs2CO3 (415 mg, 1.27 mmol), water (5 mL), and Pd(Ph3P)4 (84 mg, 0.072 mmol). 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (138 mg, 0.38 mmol) was then added and the reaction mixture was heated at 80° C. for 3 h, filtered through a pad of Celite® and the filtrate was then concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography eluting with 60% EtOAc in hexanes to afford 1-methyl-3-morpholino-4-(4-(quinolin-2-ylmethoxy)phenyl)-1H-pyrrole-2,5-dione (70 mg, 45%). 1H NMR (500 MHz, d6-DMSO): δ 8.42 (d, J=7.2 Hz, 1H), 8.1 (t, J=7.2 Hz, 2H) 7.78 (t, J=7.8 Hz, 1H), 7.70 (d, J=7.2 Hz, 1H), 7.64 (t, J=7.2 Hz, 1H), 7.28 (d, J=7.4 Hz, 2H), 7.12 (d, J=7.4 Hz, 2H), 5.38 (s, 2H), 3.62-3.58 (m, 4H), 3.45-3.39 (m, 4H), 2.96 (s, 3H); MS: M+H: m/z=430.2 HPLC: 96%, (Condition-C).

Workup

  1. filtrationfiltered through a pad of Celite®
  2. concentrationthe filtrate was then concentrated in vacuo
  3. customto obtain the crude product
  4. customThe crude material was purified via silica gel column chromatography
  5. washeluting with 60% EtOAc in hexanes

Sources & evidence

ORD record
ord-b10e72860c9d4ba1b00c3c7da58ae343
Source dataset
uspto-grants-2011_12
Patent number
US08071595B2

Reaction notes

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