Morpholine → HCID 68183034, compound

HRID 1615560Notes

Reaction equation

HRID 1615560 reaction equation
[CH2:1]([C:4]1([C:23]([O:25][CH3:26])=[O:24])[NH:9][C:8](=[O:10])[C:7]2[S:11][C:12](Br)=[CH:13][C:6]=2[CH:5]1[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[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]([C:4]1([C:23]([O:25][CH3:26])=[O:24])[NH:9][C:8](=[O:10])[C:7]2[S:11][C:12]([N:75]3[CH2:80][CH2:79][O:78][CH2:77][CH2:76]3)=[CH:13][C:6]=2[CH:5]1[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[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 68182994HCID 68182994, compound

Product 1

HCID 68183034HCID 68183034, compoundYield 26%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 5-allyl-2-bromo-4-(3,4-dichlorophenyl)-7-oxo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-5-carboxylate (0.51 g, 1.1 mmol),tris(dibenzylideneacetone)dipalladium(0) (98.3 mg, 0.107 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (124 mg, 0.215 mmol) and cesium carbonate (1.29 g, 3.97 mmol) was evacuated and filled with argon, followed by addition of 1,4-dioxane (12 mL) and morpholine (0.281 mL, 3.22 mmol). The mixture was heated at 100° C. overnight. The mixture was then concentrated in vacuo and the residue was purified by silica gel chromatography. Final purification by HPLC afforded pure product as a white solid (0.136 g, 26%). LCMS (AA) ES+: 482, 484. 1H NMR (400 MHz, DMSO) δ 7.55 (d, J=8.4 Hz, 1H), 7.31 (d, J=2.0 Hz, 1H), 7.22 (s, 1H), 7.07 (dd, J=8.4, 2.0 Hz, 1H), 5.98 (s, 1H), 5.70 (dt, J=17.0, 7.2 Hz, 1H), 5.06 (t, J=13.4 Hz, 2H), 4.41 (s, 1H), 3.66 (t, J=4.7 Hz, 4H), 3.41 (s, 3H), 3.19-3.05 (m, 4H), 2.68 (ddd, J=31.0, 13.9, 7.4 Hz, 2H).

Workup

  1. customwas evacuated
  2. additionfilled with argon
  3. concentrationThe mixture was then concentrated in vacuo
  4. customthe residue was purified by silica gel chromatography
  5. customFinal purification by HPLC

Sources & evidence

ORD record
ord-5bf018b1c7fd4abe945f69a9a781b985
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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