3-Pyridinemethanamine → N-(4-Methyl-3-{1-methyl-2-oxo-7-[(pyridin-3-ylmethyl)-amino]-1,2-dihydro-[1,6]naphthyridin-3-yl}-phenyl)-3-trifluoromethyl-benzamide

HRID 270715Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 270715
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:14]3[CH:15]=[C:16]([NH:21][C:22](=[O:33])[C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)[CH:17]=[CH:18][C:19]=3[CH3:20])[C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][N:3]=1.[NH2:34][CH2:35][C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1.[Cl-].C(C1C=CC=C(C(C)C)C=1[N+]1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C=1)(C)C>O1CCOCC1>[CH3:20][C:19]1[CH:18]=[CH:17][C:16]([NH:21][C:22](=[O:33])[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:32])[F:31])[CH:24]=2)=[CH:15][C:14]=1[C:7]1[C:8](=[O:13])[N:9]([CH3:12])[C:10]2[C:5]([CH:6]=1)=[CH:4][N:3]=[C:2]([NH:34][CH2:35][C:36]1[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=1)[CH:11]=2

Komponenten

5

Edukt 3

HCID 310183-PyridinemethanamineHCID 27349131,3-Bis(2,6-diisopropylphenyl)imidazolium chlorideHCID 59833848Benzamide,n-[3-(7-chloro-1,2-dihydro-1-methyl-2-oxo-1,6-naphthyridin-3-yl)-4-methylphenyl]-3-(trifluoromethyl)-

Produkt 1

HCID 59833940N-(4-Methyl-3-{1-methyl-2-oxo-7-[(pyridin-3-ylmethyl)-amino]-1,2-dihydro-[1,6]naphthyridin-3-yl}-phenyl)-3-trifluoromethyl-benzamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

N-[3-(7-Chloro-1-methyl-2-oxo-1,2-dihydro-[1,6]naphthyridin-3-yl)-4-methyl-phenyl]-3-trifluoromethyl-benzamide (50 mg, 0.106 mmol) is mixed with 3-(aminomethyl)-pyridine (18 mg, 0.16 mmol), Pd2(dba)2 (2.4 mg, 2.5%), 1,3-Bis(2,6-di-i-propylphenyl)-imidazolium chloride (2.3 mg, 5%) and potassium tert-butanoxide (17.8 mg, 0.159 mmol) under an argon environment. 6 mL of anhydrous 1,4-dioxane is added and the reaction is continued at 100° C. for 14 hours. After cooling and removal of solvent under vacuum, the crude product is dissolved in DMSO and purified by reverse phase preparative HPLC to give the final product as a pale solid: 1H NMR 400 MHz (DMSO-d6) δ 10.46 (s, 1H), 8.79 (s, 1H), 8.68 (d, 1H, J=4.6 Hz), 8.44 (s, 1H), 8.29 (s, 1H), 8.24 (t, 2H, J=7.5 Hz), 7.96 (d, 2H, J=7.8 Hz), 7.76 (m, 3H), 7.65 (m, 2H), 7.24 (d, 1H, J=8.3 Hz), 6.46 (s, 1H), 4.74 (s, 2H), 3.52 (s, 3H), 2.11 (s, 3H); MS m/z 544.3 (M+1).

Aufarbeitung

  1. temperatureAfter cooling
  2. customremoval of solvent under vacuum
  3. dissolutionthe crude product is dissolved in DMSO
  4. custompurified by reverse phase preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-303fec6bc46e41e98819c7cf2db26445
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07449582B2

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