Trifluoroacetic anhydride → 4-(4-Fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)-5-methylthieno[2,3-d]pyrimidine-6-carbonitrile

HRID 450583Notes

Reaction equation

HRID 450583 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]([NH2:21])=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.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl.N1C=CC=CC=1>[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]#[N: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 2

HCID 9845Trifluoroacetic anhydrideHCID 461826624-(4-Fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxamide

Product 1

HCID 461822594-(4-Fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)-5-methylthieno[2,3-d]pyrimidine-6-carbonitrileYield 68%

Reagents, catalysts & solvents 1

HCID 21875418Pyridine methylene chlorideSolvent

Procedure

To a stirred suspension of 4-(4-fluoro-2-(tetrahydro-2H-pyran-4-yloxy)phenylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxamide (0.1 g, 0.25 mmol) in DCM/pyridine (2.5 mL; 4:1) was added trifluoroacetic anhydride (0.138 mL, 1.0 mmol) at 0° C. and the mixture stirred for 4 hours. The reaction was quenched with ice and adjusted to pH 7 with saturated sodium hydrogen carbonate solution. The mixture was partitioned between DCM (10 mL) and water (10 mL). The aqueous phase was washed with DCM (10 mL) and the combined organic layers dried (MgSO4) filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (DCM→49:1 DCM/MeOH) to give the title compound as a pale yellow solid (0.065 g, 68%) after crystallisation from MeOH.

Workup

  1. customThe reaction was quenched with ice
  2. customThe mixture was partitioned between DCM (10 mL) and water (10 mL)
  3. washThe aqueous phase was washed with DCM (10 mL)
  4. dry with materialthe combined organic layers dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash column chromatography (DCM→49:1 DCM/MeOH)

Sources & evidence

ORD record
ord-52d3a7c6444d4453888f9d7a79a48fd1
Source dataset
uspto-grants-2013_07
Patent number
US08486953B2

Reaction notes

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