1-(3-Fluoro-4-(6-methoxy-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea → 1-(3-Fluoro-4-(5-methyl-6-(2-morpholinoethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea, hydrochloride salt

HRID 2117102

Reaktionsgleichung

Reaktionsgleichung von HRID 2117102
[ClH:1].FC1C=C(NC(=O)CC(NC2C=CC(F)=CC=2)=O)C=CC=1OC1C2=C(C)C(OC[CH2:21][N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=CN2N=CN=1.[F:43][C:44]1[CH:45]=[C:46]([NH:63][C:64]([NH:66][C:67](=[O:76])[CH2:68][C:69]2[CH:74]=[CH:73][C:72]([F:75])=[CH:71][CH:70]=2)=[S:65])[CH:47]=[CH:48][C:49]=1[O:50][C:51]1[C:56]2=[C:57]([CH3:62])[C:58]([O:60][CH3:61])=[CH:59][N:55]2[N:54]=[CH:53][N:52]=1>C1COCC1>[ClH:1].[F:43][C:44]1[CH:45]=[C:46]([NH:63][C:64]([NH:66][C:67](=[O:76])[CH2:68][C:69]2[CH:70]=[CH:71][C:72]([F:75])=[CH:73][CH:74]=2)=[S:65])[CH:47]=[CH:48][C:49]=1[O:50][C:51]1[C:56]2=[C:57]([CH3:62])[C:58]([O:60][CH2:61][CH2:21][N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:59][N:55]2[N:54]=[CH:53][N:52]=1

Komponenten

4

Edukt 2

HCID 116271861-(3-Fluoro-4-(6-methoxy-5-methylpyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea2×HCID 131727132N1-(3-Fluoro-4-(5-methyl-6-(2-morpholinoethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide, hydrochloride salt2×

Produkt 1

HCID 1317262391-(3-Fluoro-4-(5-methyl-6-(2-morpholinoethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea, hydrochloride saltAusbeute 30 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 3-fluoro-4-(5-methyl-6-(2-morpholinoethoxy)pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)benzenamine (30 mg, 0.072 mmol, Compound C of Example 36) in 1 mL of THF was added 2-(4-fluorophenyl)ethanoyl isothiocyanate (19 mg, 0.1 mmol, Compound A of Example 2). The solution was allowed to stir at room temperature for 2 h and HPLC analysis indicated the completion of the reaction. The reaction was then quenched with NH3 in propanol and the resulting solution was loaded on a preparative HPLC to be purified. Following a work-up procedure similar to that for Compound D of Example 36, the title compound (13 mg, 30%) was obtained as a HCl salt. 1H NMR (DMSO-d6) δ 12.45 (s, 1H), 11.85 (s, 1H), 11.50 (br s, 1H), 8.15 (s, 1H), 8.10 (s, 1H), 7.90 (d, 1H), 7.50 (m, 2H), 7.40 (m, 2H), 7.20 (m, 2H), 4.50 (br s, 2H), 4.00 (m, 2H), 3.85 (s, 2H), 3.25-3.70 (m, 8H), 2.40 (s, 3H); MS(ESI+) m/z 583.2 (M+H)+.

Aufarbeitung

  1. customthe completion of the reaction
  2. customThe reaction was then quenched with NH3 in propanol
  3. customto be purified

Quellen und Nachweise

ORD-Eintrag
ord-14a69f8717ad429d97d864874661efe2
Quelldatensatz
uspto-grants-2008_10
Patentnummer
US07439246B2

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