Morpholine → HCID 56971358, compound

HRID 1615527Notes

Reaction equation

HRID 1615527 reaction equation
Br[C:2]1[S:19][C:5]2[C:6](=[O:18])[N:7]([CH3:17])[CH2:8][CH:9]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.O1CCOCC1.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>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]>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([CH:9]2[CH2:8][N:7]([CH3:17])[C:6](=[O:18])[C:5]3[S:19][C:2]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[CH:3][C:4]2=3)=[CH:11][CH:12]=1

Participants

7

Reactant 5

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 68183342HCID 68183342, compound

Product 1

HCID 56971358HCID 56971358, compoundYield 19.7%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
140 °C

Procedure

To a 2.0-5.0 mL microwave vial was added a solution of 2-bromo-4-(4-chlorophenyl)-6-methyl-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (0.0400 g, 0.112 mmol) and morpholine (0.02934 mL, 0.3364 mmol) in anhydrous 1,4-dioxane (1.500 mL, 19.22 mmol) and degassed under nitrogen for 10 min. Cesium carbonate (0.1700 g, 0.5216 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.0195 g, 0.0336 mmol) were added followed by tris(dibenzylideneacetone)dipalladium(0) (0.0103 g, 0.0112 mmol). The reaction mixture was sealed and heated via microwave to 140° C. and allowed to stir for 40 minutes. 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 submitted for HPLC purification to afford the product (0.0080 g, 19.0%) as a white solid. LC/MS (AA) ES+ 361, 363, 365. 1H NMR (dmso-d6, 400 MHz): d 7.51 (1H, s), 7.41-7.39 (2H, m), 7.25-7.23 (2H, m), 5.03 (1H, J=4.80, Hz, t), 3.80-3.66 (5H, m), 3.46-3.40 (1H, m), 3.11-3.09 (4H, m), 2.84 (3H, s).

Workup

  1. customdegassed under nitrogen for 10 min
  2. customThe reaction mixture was sealed
  3. temperatureThe reaction was cooled to ambient temperature
  4. customquenched by the addition of a solution of saturated aqueous solution of sodium bicarbonate (10.0 mL)
  5. extractionextracted with EtOAc (10.0 mL×3)
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was submitted for HPLC purification

Sources & evidence

ORD record
ord-0b75380d52944832827c7900ad53750a
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

Loading…