3-Iodotoluene → 6-Oxo-7-phenyl-3-m-tolylamino-6,7-dihydrothieno[2,3-b]pyridine-2-carbonitrile

HRID 1455531Notes

Reaction equation

HRID 1455531 reaction equation
[NH2:1][C:2]1[C:10]2[CH:9]=[CH:8][C:7](=[O:11])[N:6]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:5]=2[S:4][C:3]=1[C:18]#[N:19].I[C:21]1[CH:22]=[C:23]([CH3:27])[CH:24]=[CH:25][CH:26]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.CN(C)CCO>[O:11]=[C:7]1[N:6]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:5]2[S:4][C:3]([C:18]#[N:19])=[C:2]([NH:1][C:21]3[CH:22]=[C:23]([CH3:27])[CH:24]=[CH:25][CH:26]=3)[C:10]=2[CH:9]=[CH:8]1

Participants

6

Reactant 3

HCID 122683-IodotolueneHCID 62657Potassium Phosphate, TribasicHCID 11161476HCID 11161476, compound

Product 1

HCID 116890016-Oxo-7-phenyl-3-m-tolylamino-6,7-dihydrothieno[2,3-b]pyridine-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 79022-(Dimethylamino)ethanolSolvent

Conditions

Temperature
80 °C

Procedure

The compound of Example 3 (5.00 g), 3-iodotoluene (4.85 ml), copper(I) iodide (0.36 g), K3PO4 (7.90 g), and N,N-dimethylethanolamine (50 ml) were placed in a pre-dried 250 ml round-bottom flask fitted with a reflux condenser. The flask was sealed, then evacuated and back-filled with nitrogen three times. The white/pink suspension was stirred by the action of a magnetic stirring bar and heated to 80° C. The reaction developed into a brown suspension and then on to a brown solution. After 1.5 hours at this temperature the reaction was shown to be complete by hplc. The reaction was cooled to room temperature, quenched by the addition of 100 ml of water, and stirred for a further 1 h at room temperature. Filtration of the resultant suspension, washing with a further 100 ml of water, gave, after drying, a crude green/brown solid (6.78 g). The crude product (6.00 g) was recrystallised from 4 volumes of AcOH, washed with EtOAc (50 ml) and then dried under vacuum to give the title compound as a yellow solid (4.16 g). δH (DMSO-d6) 7.60-7.70 (3H m), 7.40 (2H m), 7.35 (1H, d, J 9.7 Hz), 7.25 (1H, m), 6.85-7.00 (3H, m), 6.50 (1H d, J 9.7 Hz), 6.40 (1H, s), 2.35 (3H, s). LCMS (ES+) RT 3.85 minutes, 358 (M+H)+.

Workup

  1. customfitted with a reflux condenser
  2. customThe flask was sealed
  3. customevacuated
  4. additionback-filled with nitrogen three times
  5. temperatureThe reaction was cooled to room temperature
  6. customquenched by the addition of 100 ml of water
  7. stirringstirred for a further 1 h at room temperature
  8. filtrationFiltration of the resultant suspension
  9. washwashing with a further 100 ml of water
  10. customgave
  11. customafter drying
  12. customThe crude product (6.00 g) was recrystallised from 4 volumes of AcOH
  13. washwashed with EtOAc (50 ml)
  14. customdried under vacuum

Sources & evidence

ORD record
ord-f0d3b0ce479c48bbb980822c0b14961a
Source dataset
uspto-grants-2009_01
Patent number
US07482452B2

Reaction notes

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