Morpholine → 1-(3-Methanesulfonyl-phenyl)-2-methyl-5-(4-morpholin-4-yl-phenyl)-1h-pyrrole-3-carboxylic acid ethyl ester

HRID 18641Notes

Reaction equation

HRID 18641 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:14]=3)[C:11]([CH3:23])=[C:10]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:9]=2)=[CH:4][CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:27]([O:26][C:24]([C:10]1[CH:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[CH:3][CH:4]=2)[N:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH3:22])(=[O:21])=[O:20])[CH:14]=2)[C:11]=1[CH3:23])=[O:25])[CH3:28]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 24895704Ethyl 5-(4-bromophenyl)-2-methyl-1-[3-(methylsulfonyl)phenyl]-1h-pyrrole-3-carboxylate

Product 1

HCID 248957101-(3-Methanesulfonyl-phenyl)-2-methyl-5-(4-morpholin-4-yl-phenyl)-1h-pyrrole-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture of Example 2 (0.05 g, 0.108 mmol), morpholine (0.023 g, 0.24 mmol), Pd2(dba)3 (0.002 g), BINAP (0.0035 g) and sodium tert-butoxide (0.017 g) in 5 mL of toluene heated to 90° C. and stirred for 18 hours. After cooling, the mixture was filtered through diatomaceous earth, concentrated under reduced pressure and purified by flash chromatography using a gradient of ethyl acetate (0-50%) in DCM to provide the titled compound. 1H NMR (CDCl3) δ ppm 1.31 (3H), 2.20 (3H), 2.80 (3H), 3.1 (4H), 3.70 (4H), 4.25 (2H), 6.71 (2H), 6.80 (1H), 7.30-7.90 (6H); MS (ESI) m/z 469 (M+H).

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered through diatomaceous earth
  3. concentrationconcentrated under reduced pressure
  4. custompurified by flash chromatography

Sources & evidence

ORD record
ord-e30a284255914de8b1b5f71d089dd67f
Source dataset
uspto-grants-2010_06
Patent number
US07741364B2

Reaction notes

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