Morpholine → Methyl 6-allyl-4-(3,4-dichlorophenyl)-2-(morpholin-4-yl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate

HRID 1615556Notes

Reaction equation

HRID 1615556 reaction equation
[CH2:1]([N:4]1[CH:9]([C:10]([O:12][CH3:13])=[O:11])[CH:8]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[C:7]2[CH:22]=[C:23](Br)[S:24][C:6]=2[C:5]1=[O:26])[CH:2]=[CH2:3].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH:75]1[CH2:80][CH2:79][O:78][CH2:77][CH2:76]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].O1CCOCC1>[CH2:1]([N:4]1[CH:9]([C:10]([O:12][CH3:13])=[O:11])[CH:8]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[C:7]2[CH:22]=[C:23]([N:75]3[CH2:80][CH2:79][O:78][CH2:77][CH2:76]3)[S:24][C:6]=2[C:5]1=[O:26])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 68183088Methyl 6-allyl-2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate

Product 1

HCID 68183133Methyl 6-allyl-4-(3,4-dichlorophenyl)-2-(morpholin-4-yl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylateYield 63.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 6-allyl-2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate (0.63 g, 1.3 mmol), tris(dibenzylideneacetone)dipalladium(0) (64.7 mg, 0.0706 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (80.7 mg, 0.139 mmol) and cesium carbonate (1.30 g, 3.98 mmol) was evacuated and filled with argon, followed by addition of 1,4-dioxane (37 mL) and morpholine (0.347 mL, 3.98 mmol). The mixture was heated in a sealed microwave tube at 100° C. for 10 h. The mixture was dry loaded on silica gel and purified by chromatography to afford the product as a white solid (0.398 g, 62%). LCMS: (AA) ES+: 481, 483, 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J=8.3 Hz, 1H), 7.20 (d, J=2.1 Hz, 1H), 6.92 (dd, J=8.3, 2.1 Hz, 1H), 5.71 (s, 1H), 5.36-5.22 (m, 1H), 5.00-4.90 (m, 2H), 4.78 (dd, J=15.2, 4.9 Hz, 1H), 4.55 (s, 1H), 4.12 (t, J=3.0 Hz, 1H), 3.85-3.77 (m, 4H), 3.73 (d, J=8.0 Hz, 3H), 3.42-3.31 (m, 1H), 3.18 (dd, J=12.0, 7.1 Hz, 4H).

Workup

  1. customwas evacuated
  2. additionfilled with argon
  3. customThe mixture was dry
  4. custompurified by chromatography

Sources & evidence

ORD record
ord-fa1c45556fdd4e398edaa3139645dbae
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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