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

HRID 394752Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 394752
[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

Komponenten

10

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-5533adaadb32479fa8dc892c6b292ce5
Quelldatensatz
uspto-grants-2003_08
Patentnummer
US06602863B1

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