p-Toluenesulfonic acid → Methyl 4-(4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)thieno[2,3-d]pyrimidine-6-carboxylate

HRID 450548Notes

Reaction equation

HRID 450548 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[F:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([O:23][CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:17]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[F:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:2]2[C:3]3[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)=[C:18]([O:23][CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:17]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 17965841Methyl 4-chlorothieno[2,3-d]pyrimidine-6-carboxylateHCID 584130794-Fluoro-2-(oxan-4-yloxy)aniline

Product 1

HCID 46182082Methyl 4-(4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)thieno[2,3-d]pyrimidine-6-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Methyl 4-chlorothieno[2,3-d]pyrimidine-6-carboxylate (0.256 g, 1.12 mmol), 4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)aniline (0.236 g, 1.12 mmol) and para-toluene sulfonic acid (0.021 g, 0.01 mmol) were heated at reflux in anhydrous 1,4-dioxane (6 mL) for 4 hours. The solution was cooled, concentrated in vacuo and the crude product absorbed on to silica. The sample was purified by flash column chromatography (100% DCM→10% MeOH/DCM) to yield the title compound (0.220 g, 49%) after recrystallisation from MeOH.

Workup

  1. temperatureThe solution was cooled
  2. concentrationconcentrated in vacuo
  3. customthe crude product absorbed on to silica
  4. customThe sample was purified by flash column chromatography (100% DCM→10% MeOH/DCM)

Sources & evidence

ORD record
ord-9138ab012659496ebd1435dcbcff1139
Source dataset
uspto-grants-2013_07
Patent number
US08486953B2

Reaction notes

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