Trifluoroacetic acid → N-(4-m-Tolylamino-pyrido[3,4-d]pyrimidin-6-yl)-acrylamide

HRID 394752Notes

Reaction equation

HRID 394752 reaction equation
[NH2:1][C:2]1[N:19]=[CH:18][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[CH:12]=3)[C:4]=2[CH:3]=1.NC1C=CC=C(C)C=1.ClC1C2C=C(F)N=CC=2N=CN=1.C[O:41][C:42]1C=CC(CN)=[CH:44][CH:43]=1.FC(F)(F)C(O)=O.C(Cl)(=O)C=C>CN(C1C=CN=CC=1)C.O.CCN(CC)CC>[CH3:17][C:13]1[CH:12]=[C:11]([NH:10][C:9]2[C:4]3[CH:3]=[C:2]([NH:1][C:42](=[O:41])[CH:43]=[CH2:44])[N:19]=[CH:18][C:5]=3[N:6]=[CH:7][N:8]=2)[CH:16]=[CH:15][CH:14]=1

Participants

10

Reactant 6

HCID 6422Trifluoroacetic acidHCID 7934m-ToluidineHCID 13140Acryloyl chlorideHCID 754524-MethoxybenzylamineHCID 53283756-Amino-4-[(3-methylphenyl)amino]pyrido[3,4-d]pyrimidineHCID 106790414-CHLORO-6-FLUOROPYRIDO[3,4-D]PYRIMIDINE

Product 1

HCID 10662351N-(4-m-Tolylamino-pyrido[3,4-d]pyrimidin-6-yl)-acrylamideYield 24%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
20 °C

Procedure

To a stirred solution of 6-amino-4-[(3-methylphenyl)amino]pyrido[3,4-d]pyrimidine, made from m-toluidine and 4-chloro-6-fluoropyrido[3,4-d]-pyrimidine, followed by p-methoxybenzylamine and trifluoroacetic acid, as described in the previous example (140 mg, 0.56 mmol), DMAP (14 mg) and Et3N (excess, 0.5 mL) at 0° C. under N2 was added acryloyl chloride (2.7 mol eq., 123 μL) dropwise over 3 hours. The reaction was then stirred at 20° C. for 1 hour, diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure before being chromatographed on silica gel eluting with CH2Cl2/EtOAc (1:1) to MeOH/CH2Cl2/EtOAc (2:48:50), to give N-[4-[(3-methylphenyl)amino]pyrido-[3,4-d]pyrimidin-6-yl]acrylamide (41 mg, 24%) as a cream powder, mp (EtOAc/hexane) 221-223° C. (decomp).

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. custombefore being chromatographed on silica gel eluting with CH2Cl2/EtOAc (1:1) to MeOH/CH2Cl2/EtOAc (2:48:50)

Sources & evidence

ORD record
ord-5533adaadb32479fa8dc892c6b292ce5
Source dataset
uspto-grants-2003_08
Patent number
US06602863B1

Reaction notes

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