Aniline → 5-morpholino-7-oxo-N-phenyl-7H-thieno[3,2-b]pyran-3-carboxamide

HRID 1042026Notes

Reaction equation

HRID 1042026 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.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[NH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.N12CCCN=C1CCCCC2.[O:54]1CCC[CH2:55]1>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd]>[O:15]1[CH2:16][CH2:17][N:12]([C:8]2[O:7][C:6]3[C:2]([C:55]([NH:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[O:54])=[CH:3][S:4][C:5]=3[C:10](=[O:11])[CH:9]=2)[CH2:13][CH2:14]1

Participants

8

Reactant 5

HCID 6115AnilineHCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 441811783-Bromo-5-(morpholin-4-yl)-7H-thieno[3,2-b]pyran-7-one

Product 1

HCID 441805145-morpholino-7-oxo-N-phenyl-7H-thieno[3,2-b]pyran-3-carboxamide

Reagents, catalysts & solvents 2

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)Catalyst

Conditions

Temperature
125 °C

Procedure

A 2 mL microwave vial was charged with a magnetic stirring bar, 3-bromo-5-morpholino-7H-thieno[3,2-b]pyran-7-one (103) (100 mg, 316 μmol), molybdenumhexacarbonyl (42 mg, 160 μmol), trans-di(μ-acetato)bis[o-(di-o-tolyl-phosphino)benzyl]dipalladium (II) (4.6 mg, 4.9 μmol), tri-tert-butylphosphonium tetrafluoroborate (2.8 mg, 12.0 μmol), tetrahydrofuran (500 μL), aniline (45 μL, 483 μmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (32 μL, 210 μmol). The vial was immediately sealed, magnetically stirred and heated via microwave irradiation to 125° C. for 6 minutes. The mixture was cooled to room temperature, and loaded onto Isolute functionalized silica column (PE-AX/SCX-2). The column was washed with methanol and the product was eluted with 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-7-oxo-N-phenyl-7H-thieno[3,2-b]pyran-3-carboxamide (51), (3.88 mg, 10.9 μmol) as a yellow solid.

Workup

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

Sources & evidence

ORD record
ord-58e2dfdbc27a44d9b300597ec4e1c0e0
Source dataset
uspto-grants-2013_10
Patent number
US08557807B2

Reaction notes

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