3-(Trifluoromethyl)benzoic acid → N-{3-[2-(4-Chloro-phenylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-4-methyl-phenyl}-3-trifluoromethyl benzamide

HRID 1853951

Reaktionsgleichung

Reaktionsgleichung von HRID 1853951
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:26])=[C:6]([N:8]2[CH2:25][CH2:24][C:11]3[N:12]=[C:13]([NH:16][C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=4)[N:14]=[CH:15][C:10]=3[CH2:9]2)[CH:7]=1.[F:27][C:28]([F:39])([F:38])[C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=1)[C:32](O)=[O:33].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C.C(OCC)(=O)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:13]2[N:14]=[CH:15][C:10]3[CH2:9][N:8]([C:6]4[CH:7]=[C:2]([NH:1][C:32](=[O:33])[C:31]5[CH:35]=[CH:36][CH:37]=[C:29]([C:28]([F:27])([F:38])[F:39])[CH:30]=5)[CH:3]=[CH:4][C:5]=4[CH3:26])[CH2:25][CH2:24][C:11]=3[N:12]=2)=[CH:18][CH:19]=1

Komponenten

7

Edukt 4

HCID 99633-(Trifluoromethyl)benzoic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68253436[6-(5-Amino-2-methyl-phenyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-(4-chloro-phenyl)amine

Produkt 1

HCID 67328929N-{3-[2-(4-Chloro-phenylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-4-methyl-phenyl}-3-trifluoromethyl benzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of [6-(5-Amino-2-methyl-phenyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-(4-chloro-phenyl)amine (54.87 mg, 0.15 mmol), 3-Trifluoromethylbenzoic acid (28.51 mg, 0.15 mmol), and Diisipropylethylamine (DIPEA) (78 μl, 0.45 mmol) in DMF (7.5 ml) was added 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (59 mg, 0.15 mmol) and the reaction mixture is stirred for 3 hour at room temperature. The reaction mixture was diluted with ethyl acetate and washed with 5% aqueous sodium bisulphate solution, saturated aqueous sodium bicarbonate solution and brine. The organic layer is dried over sodium sulphate and concentrated under reduced pressure. The crude product obtained was purified by column chromatography (SiO2, 2-10% methanol in chloroform to give of N-{3-[2-(4-chlorophenylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-4-methyl-phenyl}-3-trifluoromethylbenzamide [13] as a pale yellow solid. [Yield: 60.6 mg, 75.2%]

Aufarbeitung

  1. washwashed with 5% aqueous sodium bisulphate solution, saturated aqueous sodium bicarbonate solution and brine
  2. dry with materialThe organic layer is dried over sodium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product obtained
  5. customwas purified by column chromatography (SiO2, 2-10% methanol in chloroform

Quellen und Nachweise

ORD-Eintrag
ord-6d8ca7af58ec4bdebdfde2ff36ac2ef0
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962637B2

Verknüpfte Notizen

Wird geladen…