Trifluoroacetic acid → 4-(2-(4-Cyanophenylamino)thieno[2,3-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile

HRID 2188987Notes

Reaction equation

HRID 2188987 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:11][C:12]2[C:19]([CH3:20])=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=2[CH3:21])[C:5]2[CH:10]=[CH:9][S:8][C:6]=2[N:7]=1.C(O)(C(F)(F)F)=O.[NH2:29][C:30]1[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=1>C(OCC)(=O)C>[C:34]([C:33]1[CH:36]=[CH:37][C:30]([NH:29][C:2]2[N:3]=[C:4]([O:11][C:12]3[C:19]([CH3:20])=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=3[CH3:21])[C:5]3[CH:10]=[CH:9][S:8][C:6]=3[N:7]=2)=[CH:31][CH:32]=1)#[N:35]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 133964-AminobenzonitrileHCID 578488784-(2-Chlorothieno[2,3-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile

Product 1

HCID 247950814-(2-(4-Cyanophenylamino)thieno[2,3-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrileYield 14.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-(2-chlorothieno[2,3-d]pyrimidin-4-yloxy)-3,5-dimethylbenzonitrile (188 mg, 0.59 mmol), TFA (0.37 mL, 4.75 mmol) in TFE (2.5 mL) was added 4-aminobenzonitrile (280 mg, 2.37 mmol) in a sealed tube. The reaction was stirred at 90° C. for 2 d. Reaction mixture was diluted with ethyl acetate (5 mL) and washed with saturated NaHCO3 (3×10 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by HPLC afforded the product as white solid (34 mg, 14%):

Workup

  1. customReaction mixture
  2. washwashed with saturated NaHCO3 (3×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-929239d62ae042dbb487f9c30ed98b1e
Source dataset
uspto-grants-2012_12
Patent number
US08324223B2

Reaction notes

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