Morpholine → HCID 68182979, compound

HRID 1615563Notes

Reaction equation

HRID 1615563 reaction equation
[CH2:1]([N:4]1[CH2:9][CH:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=2)[C:7]2[CH:18]=[C:19](Br)[S:20][C:6]=2[C:5]1=[O:22])[CH:2]=[CH2:3].[NH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[Cs+].[Cs+].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>O1CCOCC1.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]>[CH2:1]([N:4]1[CH2:9][CH:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=2)[C:7]2[CH:18]=[C:19]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[S:20][C:6]=2[C:5]1=[O:22])[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 68183196HCID 68183196, compound

Product 1

HCID 68182979HCID 68182979, compoundYield 108.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
140 °C

Procedure

A solution of 6-allyl-2-bromo-4-(3,4-dichlorophenyl)-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (0.02 g, 0.05 mmol) and morpholine (0.01 mL, 0.14 mmol) in anhydrous 1,4-dioxane (2.00 mL) was degassed under nitrogen for 10 min. Cesium carbonate (72.7 mg, 0.22 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (8.32 mg, 0.01 mmol) was added followed by tris(dibenzylideneacetone)dipalladium(0) (4.4 mg, 0.0048 mmol). The reaction mixture was heated to 140° C. for 1 hour by microwave irradiation. The reaction was cooled to ambient temperature and quenched by the addition of a solution of saturated aqueous solution of sodium bicarbonate (10.0 mL) and extracted with EtOAc (10.0 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (4 g cartridge, gradient hexanes to 100% EtOAc) to afford the product (22.9 mg, 68%) as a yellow oil. LCMS (AA): ES+ 423, 425, 427. 1H NMR (DMSO-d6, 400 MHz): δ 7.59 (d, J=8.4 Hz, 1H), 7.49 (d, J=2.0 Hz, 1H), 7.16 (dd, J=8.4, 2.0 Hz, 1H), 5.83 (s, 1H), 5.66-5.59 (m, 1H), 5.09-5.05 (m, 2H), 4.30 (t, J=6.0 Hz, 1H), 3.99-3.84 (m, 2H), 3.75-3.68 (m, 5H), 3.70-3.45 (m, 1H), 3.13-3.10 (m, 4H).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customquenched by the addition of a solution of saturated aqueous solution of sodium bicarbonate (10.0 mL)
  3. extractionextracted with EtOAc (10.0 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by silica gel column chromatography (4 g cartridge, gradient hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-84470077a53b4b6f928366f81fb01757
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

Loading…