p-Toluenesulfonic acid → 4-[4-Fluoro-2-(tetrahydro-pyran-4-yloxy)-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methylester

HRID 450533Notes

Reaction equation

HRID 450533 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([O:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:3]=1.Cl[C:17]1[C:18]2[C:25]([CH3:26])=[C:24]([C:27]([O:29][CH3:30])=[O:28])[S:23][C:19]=2[N:20]=[CH:21][N:22]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:17]2[C:18]3[C:25]([CH3:26])=[C:24]([C:27]([O:29][CH3:30])=[O:28])[S:23][C:19]=3[N:20]=[CH:21][N:22]=2)=[C:4]([O:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:3]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 2759834Methyl 4-chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylateHCID 584130794-Fluoro-2-(oxan-4-yloxy)aniline

Product 1

HCID 461820444-[4-Fluoro-2-(tetrahydro-pyran-4-yloxy)-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methylesterYield 90.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

4-Fluoro-2-(tetrahydro-2H-pyran-4-yloxy)aniline (3.47 g, 16.4 mmol), methyl 4-chloro-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (3.99 g, 16.4 mmol) and para-toluene sulfonic acid (0.313 g, 1.64 mmol) were heated at reflux in anhydrous 1,4-dioxane (30 mL) for 1.5 hours. The solution was cooled to ambient temperature, the precipitate collected and washed with cold 1,4-dioxane to yield the title compound as yellow solid (6.17 g, 90%).

Workup

  1. customthe precipitate collected
  2. washwashed with cold 1,4-dioxane

Sources & evidence

ORD record
ord-758f4ae9dd8f40caae2e8897119025f9
Source dataset
uspto-grants-2013_07
Patent number
US08486953B2

Reaction notes

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