Sodium Carbonate → 3-(1-Methylindol-3-yl)-4-[3-(2-morpholin-4-ylethyloxy)phenyl]-1-methylpyrrole-2,5-dione

HRID 1017562Notes

Reaction equation

HRID 1017562 reaction equation
[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:11]=[C:12](I)[CH:13]=[CH:14][CH:15]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:41]1[C:42](=[O:58])[N:43]([CH3:57])[C:44](=[O:56])[C:45]=1[C:46]1[C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[N:48]([CH3:55])[CH:47]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:55][N:48]1[C:49]2[C:54](=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:46]([C:45]2[C:44](=[O:56])[N:43]([CH3:57])[C:42](=[O:58])[C:41]=2[C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([O:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[CH:11]=2)=[CH:47]1

Participants

7

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 98184713-Bromo-1-methyl-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dioneHCID 184035554-[2-(3-Iodophenoxy)ethyl]morpholine

Product 1

HCID 184035183-(1-Methylindol-3-yl)-4-[3-(2-morpholin-4-ylethyloxy)phenyl]-1-methylpyrrole-2,5-dioneYield 70%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×

Conditions

Temperature
80 °C

Procedure

A flask charged with 3-(2-morpholin-4-ylethyloxy)iodobenzene (0.33 g, 1 mmol), bis(pinacolato)diboron (0.279 g, 1.1 mmol), potassium acetate (0.294 g, 3 mmol) and PdCl2(dppf) (48 mg, 0.06 mmol) was flushed with nitrogen. N,N-Dimethylformamide (6 mL) was added and the reaction mixture was stirred at 80° C. for 3h and then cooled to room temperature. 3-Bromo-4-(1-methylindol-3-yl)-1-methylpyrrole-2,5-dione (0.255 g, 0.8 mmol) ((synthesized according to the procedures described in Brenner, M. et al., Tet. Lett. 44, 2887, (1988)) was added to the reaction mixture, followed by the addition of PdCl2(dppf) (48 mg, 0.06 mmol)) and 2M aq. Na2CO3 (2.5 mL). The resulting mixture was stirred at 80° C. for 2.5 h, then cooled to room temperature, and quenched with H2O. The product was extracted with EtOAc. The EtOAc layer was washed with H2O, NaCl (sat.), dried over Na2SO4, and concentrated. Purification of the crude product on a silica gel column with 2/3/5 of acetone/CH2Cl2/hexane gave 3-(1-methylindol-3-yl)-4-[3-(2-morpholin-4-ylethyloxy)-phenyl]-1-methylpyrrole-2,5-dione as an orange-red oil. (0.25 g, 70% yield).

Workup

  1. customwas flushed with nitrogen
  2. additionN,N-Dimethylformamide (6 mL) was added
  3. temperaturecooled to room temperature
  4. addition44, 2887, (1988)) was added to the reaction mixture
  5. stirringThe resulting mixture was stirred at 80° C. for 2.5 h
  6. temperaturecooled to room temperature
  7. customquenched with H2O
  8. extractionThe product was extracted with EtOAc
  9. washThe EtOAc layer was washed with H2O, NaCl (sat.)
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customPurification of the crude product on a silica gel column with 2/3/5 of acetone/CH2Cl2/hexane

Sources & evidence

ORD record
ord-17163992a83b4ece9fbf8affdca8e367
Source dataset
uspto-grants-2002_11
Patent number
US06479490B2

Reaction notes

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