Diisopropylamine → 5-morpholino-3-(phenylethynyl)-7H-thieno[3,2-b]pyran-7-one

HRID 1042025Notes

Reaction equation

HRID 1042025 reaction equation
Br[C:2]1[C:6]2[O:7][C:8]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[CH:9][C:10](=[O:11])[C:5]=2[S:4][CH:3]=1.[C:18]1([C:24]#[CH:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(NC(C)C)(C)C>CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[O:15]1[CH2:16][CH2:17][N:12]([C:8]2[O:7][C:6]3[C:2]([C:25]#[C:24][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:3][S:4][C:5]=3[C:10](=[O:11])[CH:9]=2)[CH2:13][CH2:14]1

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 10821PhenylacetyleneHCID 441811783-Bromo-5-(morpholin-4-yl)-7H-thieno[3,2-b]pyran-7-one

Product 1

HCID 441801595-morpholino-3-(phenylethynyl)-7H-thieno[3,2-b]pyran-7-oneYield 45%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with a magnetic stirring bar, 3-bromo-5-morpholino-7H-thieno[3,2-b]pyran-7-one (103) (50 mg, 158.1 μmol), phenylacetylene (32.0 mg, 316.2 μmol), trans-dichlorobis(triphenylphosphine)palladium (II) (5.6 mg, 7.9 μmol), copper (I) iodide (1.6 mg, 7.9 μmol) and diisopropylamine (1.0 mL). The mixture was magnetically stirred and heated via microwave irradiation to 100° C. for 20 minutes. The mixture was cooled to room temperature, and then concentrated in vacuo resulting in a brown solid. The solid was dissolved in methanol (1.0 mL) and loaded onto Isolute functionalized silica column (PE-AX/SCX-2). The column was washed with methanol and 7N methanolic ammonia. The methanolic ammonia fractions were combined and concentrated in vacuo. The resulting solid was purified using preparative high-pressure liquid chromatography to give 5-morpholino-3-(phenylethynyl)-7H-thieno[3,2-b]pyran-7-one (31) (24.0 mg, 71.1 μmol) as an orange solid.

Workup

  1. additionA microwave vial was charged with a magnetic stirring bar
  2. temperatureThe mixture was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customresulting in a brown solid
  5. washThe column was washed with methanol and 7N methanolic ammonia
  6. concentrationconcentrated in vacuo
  7. customThe resulting solid was purified

Sources & evidence

ORD record
ord-7b6bc7cd15bc470187024f5766fb428f
Source dataset
uspto-grants-2013_10
Patent number
US08557807B2

Reaction notes

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