p-Toluenesulfonic acid → 5-Methyl-4-[2-(tetrahydro-pyran-4-yloxy)-pyridin-3-ylamino]-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester

HRID 450553Notes

Reaction equation

HRID 450553 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8]2[C:13]([NH2:14])=[CH:12][CH:11]=[CH:10][N:9]=2)[CH2:3][CH2:2]1.Cl[C:16]1[C:17]2[C:24]([CH3:25])=[C:23]([C:26]([O:28][CH3:29])=[O:27])[S:22][C:18]=2[N:19]=[CH:20][N:21]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[NH4+].O>O1CCOCC1>[CH3:25][C:24]1[C:17]2[C:16]([NH:14][C:13]3[C:8]([O:7][CH:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)=[N:9][CH:10]=[CH:11][CH:12]=3)=[N:21][CH:20]=[N:19][C:18]=2[S:22][C:23]=1[C:26]([O:28][CH3:29])=[O:27]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 2759834Methyl 4-chloro-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylateHCID 532566082-(tetrahydro-2H-pyran-4-yloxy)pyridin-3-amineHCID 86589665Water ammonium hydroxide

Product 1

HCID 461820865-Methyl-4-[2-(tetrahydro-pyran-4-yloxy)-pyridin-3-ylamino]-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl esterYield 47.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2-(Tetrahydro-2H-pyran-4-yloxy)pyridin-3-amine (0.99 g, 5.10 mmol), methyl 4-chloro-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (1.237 g, 5.10 mmol) and para-toluene sulfonic acid (0.097 g, 0.51 mmol) were heated at reflux in anhydrous 1,4-dioxane (20 mL) for 16 hours. The solution was cooled to ambient temperature and poured into a stirred solution of ammonium hydroxide/water (1:4). The precipitate was filtered off, washed with water, diethyl ether and dried. The product was purified by reverse phase preparative HPLC to yield grey solid (0.963 g, 47%).

Workup

  1. filtrationThe precipitate was filtered off
  2. washwashed with water, diethyl ether
  3. customdried
  4. customThe product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-e04a5df050394262a45a556431054b74
Source dataset
uspto-grants-2013_07
Patent number
US08486953B2

Reaction notes

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