Oxalyl chloride → 4-(4-Fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxamide

HRID 450540Notes

Reaction equation

HRID 450540 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]3[C:17]([CH3:18])=[C:16]([C:19]([OH:21])=O)[S:15][C:11]=3[N:12]=[CH:13][N:14]=2)=[C:4]([O:22][CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:3]=1.C(Cl)(=O)C(Cl)=O.C1COCC1.C[N:41](C=O)C>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]3[C:17]([CH3:18])=[C:16]([C:19]([NH2:41])=[O:21])[S:15][C:11]=3[N:12]=[CH:13][N:14]=2)=[C:4]([O:22][CH:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[CH:3]=1

Participants

4

Reactant 3

HCID 65578Oxalyl chlorideHCID 21974620tetrahydrofuran N,N-dimethylformamideHCID 461826634-(4-Fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxylic acid

Product 1

HCID 461826624-(4-Fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxamideYield 55.7%

Procedure

To a stirred suspension of 4-[4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)-phenylamino]-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid (0.5 g, 1.24 mmol) in THF/DMF (9.0 mL; 8:1) was added oxalyl chloride (0.33 mL, 3.7 mmol) and the mixture stirred for 18 hours. The solvent was concentrated and the residue co-evaporated with toluene. To the residue was added a solution of ammonia in dioxane (0.5 M, 20 mL) and the mixture stirred for 18 hours. The reaction mixture was diluted with 10% MeOH in DCM (50 mL) and absorbed onto silica. The crude product was chromatographed by flash column chromatography (3% MeOH in DCM) to give the product as pale yellow solid (0.278 g, 55.7%).

Workup

  1. concentrationThe solvent was concentrated
  2. additionTo the residue was added a solution of ammonia in dioxane (0.5 M, 20 mL)
  3. stirringthe mixture stirred for 18 hours
  4. additionThe reaction mixture was diluted with 10% MeOH in DCM (50 mL)
  5. customabsorbed onto silica
  6. customThe crude product was chromatographed by flash column chromatography (3% MeOH in DCM)

Sources & evidence

ORD record
ord-45479acf7ea14c33978789bff5716347
Source dataset
uspto-grants-2013_07
Patent number
US08486953B2

Reaction notes

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