Diisopropylethylamine → 1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylicacid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]amide

HRID 573412Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 573412
F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[CH2:25]([N:27]1[CH:32]=[C:31]([C:33]([OH:35])=O)[C:30](=[O:36])[N:29]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)[C:28]1=[O:44])[CH3:26].C(N(CC)C(C)C)(C)C.[CH3:54][O:55][C:56]1[CH:57]=[C:58]2[C:63](=[CH:64][C:65]=1[O:66][CH3:67])[N:62]=[CH:61][CH:60]=[C:59]2[O:68][C:69]1[CH:74]=[CH:73][C:72]([NH2:75])=[CH:71][C:70]=1[F:76]>CN(C)C=O.CCOC(C)=O>[CH3:54][O:55][C:56]1[CH:57]=[C:58]2[C:63](=[CH:64][C:65]=1[O:66][CH3:67])[N:62]=[CH:61][CH:60]=[C:59]2[O:68][C:69]1[CH:74]=[CH:73][C:72]([NH:75][C:33]([C:31]2[C:30](=[O:36])[N:29]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[C:28](=[O:44])[N:27]([CH2:25][CH3:26])[CH:32]=2)=[O:35])=[CH:71][C:70]=1[F:76]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114269974-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamineHCID 895826181-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid

Produkt 1

HCID 715567591-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylicacid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]amide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU) (0.072 g, 0.19 mmol) and 1-ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (0.053 g, 0.19 mmol) in N,N-dimethylformamide (2 mL) was added N,N-diisopropylethylamine (0.055 mL, 0.32 mmol). After 15 min stirring at rt, 4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenylamine (0.05 g, 0.2 mmol) was added. The reaction was stirred at rt for 12 h, diluted with EtOAc (25 mL), then washed with 1N Na2CO3, water and brine and then dried over MgSO4. The product was crystallized from MeOH to give 75 mg (68%) as a white solid. mp=151-4° C.; LCMS m/z=575 (M+1); 1H NMR (DMSO) δ: 11.04 (s, 1H), 8.89 (s, 1H), 8.47 (d, 1H, J=5.4 Hz), 7.98, 8.01 (dd, 1H, J=2.3, 12.6 Hz), 7.52-7.56 (m, 2H), 7.33-7.46 (m, 6H), 6.47 (d, 1H, J=5.4 Hz), 4.01 (q, 2H, J=7 Hz), 3.98 (d, 6H), 13.0 (t, 3H, J=7 Hz).

Aufarbeitung

  1. stirringThe reaction was stirred at rt for 12 h
  2. washwashed with 1N Na2CO3, water and brine
  3. dry with materialdried over MgSO4
  4. customThe product was crystallized from MeOH
  5. customto give 75 mg (68%) as a white solid

Quellen und Nachweise

ORD-Eintrag
ord-71c0a35dc06c47069a21709ecf27f2c4
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09029538B2

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