2-[4-(4-Amino-2-methoxy-phenyl)-piperidin-1-yl]-acetamide → Trifluoroacetic acid

HRID 1262144Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1262144
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([NH:9][C:10]2[N:15]=[CH:14][C:13]3=[CH:16][CH:17]=[C:18]([C:19]4[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=4)[N:12]3[N:11]=2)[CH:6]=[CH:5][C:4]=1[CH:27]1[CH2:32][CH2:31][N:30]([CH2:33][C:34]([NH2:36])=[O:35])[CH2:29][CH2:28]1.COC1N=CC(C2N3C(C=NC(OS([C:58]([F:61])([F:60])[F:59])(=O)=O)=N3)=CC=2)=CC=1.NC1C=CC(C2CCN(CC(N)=O)CC2)=C([O:79][CH3:80])C=1>>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([NH:9][C:10]2[N:15]=[CH:14][C:13]3=[CH:16][CH:17]=[C:18]([C:19]4[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=4)[N:12]3[N:11]=2)[CH:6]=[CH:5][C:4]=1[CH:27]1[CH2:32][CH2:31][N:30]([CH2:33][C:34]([NH2:36])=[O:35])[CH2:29][CH2:28]1.[C:80]([OH:79])([C:58]([F:59])([F:60])[F:61])=[O:2]

Komponenten

5

Edukt 3

HCID 667119832-[4-(4-Amino-2-methoxy-phenyl)-piperidin-1-yl]-acetamideHCID 667123102-(4-{2-Methoxy-4-[7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamideHCID 86661684Trifluoro-methanesulfonic acid 7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester

Produkt 2

HCID 6422Trifluoroacetic acidAusbeute 33 %HCID 667123102-(4-{2-Methoxy-4-[7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamide

Versuchsvorschrift

2-(4-{2-Methoxy-4-[7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamide. Trifluoro-methanesulfonic acid 7-(6-methoxy-pyridin-3-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl ester (0.138 g, 0.369 mmol; and 2-[4-(4-Amino-2-methoxy-phenyl)-piperidin-1-yl]-acetamide (0.121 g, 0.461 mmol) were reacted in an analogous manner to Example 908D at room temp for 72 h. The reaction mixture was concentrated, taken up in EtOAc, and washed with brine. The EtOAc layer was dried, filtered over MgSO4, and concentrated. The resulting residue was purified by Gilson RP-HPLC and lyophilized to afford title compound as a TFA salt (59 mg, 33%). LCMS=488.0 (M+H), HPLC rt=2.329, purity=99%. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.53 (bs, 1H), 9.47 (s, 1H), 9.02 (s, 1H), 9.00 (d, J=8.2 Hz, 1H), 8.40 (dd, J=8.7 Hz, 2.3 Hz, 1H), 7.98 (s, 1H), 7.71 (s, 1H), 7.46 (s, 1H), 7.24 (d, J=8.5 Hz, 1H), 7.17 (d, J=4.9 Hz, 1H), 7.04 (d, J=8.3 Hz, 1H0, 6.97 (d, J=4.7 Hz, 1H), 6.93 (s, 1H), 3.93 (s, 3H), 3.89 (m, 2H), 3.70 (s, 3H), 3.54 (d, J=11.7 Hz, 2H), 3.23-3.05 (m, 3H), 2.05-1.95 (m, 2H), 1.85-1.88 (m, 2H).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. washwashed with brine
  3. dry with materialThe EtOAc layer was dried
  4. filtrationfiltered over MgSO4
  5. concentrationconcentrated
  6. customThe resulting residue was purified by Gilson RP-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-372c9a3157264ba8a23d92f08edb7e4c
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08471005B2

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