Dimethylformamide → 2-(4-{4-[7-[2-(Methanesulfonyl-methyl-amino)-phenyl]-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperidin-1-yl)-acetamide

HRID 1262336

Reaktionsgleichung

Reaktionsgleichung von HRID 1262336
O[C:2]1[N:7]=[CH:6][C:5]2=[C:8]([O:23][CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[CH:9]=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:17]([CH3:22])[S:18]([CH3:21])(=[O:20])=[O:19])[N:4]2[N:3]=1.CN(C)C=O.C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.[NH2:58][C:59]1[CH:64]=[CH:63][C:62]([CH:65]2[CH2:70][CH2:69][N:68]([CH2:71][C:72]([NH2:74])=[O:73])[CH2:67][CH2:66]2)=[CH:61][C:60]=1[O:75][CH3:76]>>[CH3:21][S:18]([N:17]([CH3:22])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:10]1[N:4]2[C:5]([CH:6]=[N:7][C:2]([NH:58][C:59]3[CH:64]=[CH:63][C:62]([CH:65]4[CH2:70][CH2:69][N:68]([CH2:71][C:72]([NH2:74])=[O:73])[CH2:67][CH2:66]4)=[CH:61][C:60]=3[O:75][CH3:76])=[N:3]2)=[C:8]([O:23][CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:30])[CH3:31])[CH:9]=1)(=[O:20])=[O:19]

Komponenten

5

Edukt 4

HCID 6228DimethylformamideHCID 142176Phenyl triflimideHCID 569459622-[4-(4-Amino-3-methoxy-phenyl)-piperidin-1-yl]-acetamideHCID 178482114HCID 178482114, Verbindung

Produkt 1

HCID 667119472-(4-{4-[7-[2-(Methanesulfonyl-methyl-amino)-phenyl]-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperidin-1-yl)-acetamideAusbeute 66 %

Versuchsvorschrift

1259h. Into a 8-dram vial, N-{2-[2-Hydroxy-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-phenyl}-N-methyl-methanesulfonamide (9.0E1 mg, 0.19 mmol), N,N-Dimethylformamide (0.70 mL, 9.0 mmol) N,N-Diisopropylethylamine (0.101 mL, 0.581 mmol) and N-Phenylbis(trifluoromethanesulphonimide) (83.0 mg, 0.232 mmol) were added. The reaction mixture was stirred at room temperature for one hour. 2-[4-(4-Amino-3-methoxy-phenyl)-piperidin-1-yl]-acetamide (102 mg, 0.387 mmol) was added. The reaction was heated at 120° C. for 3 hours. The solvent was removed under vacuum. The reaction mixture was purified via ISCO column chromatography with DCM and NH3 in methanol as eluant (2 to 15% NH3 in methanol). The collected fractions afforded 2-(4-{4-[7-[2-(Methanesulfonyl-methyl-amino)-phenyl]-5-(2-trimethylsilanyl-ethoxymethoxy)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxy-phenyl}-piperidin-1-yl)-acetamide as a red oil (89 mg, 65%)

Aufarbeitung

  1. custom1259h
  2. temperatureThe reaction was heated at 120° C. for 3 hours
  3. customThe solvent was removed under vacuum
  4. customThe reaction mixture was purified via ISCO column chromatography with DCM and NH3 in methanol as eluant (2 to 15% NH3 in methanol)

Quellen und Nachweise

ORD-Eintrag
ord-8f9d96af44ac4055a611cfbdae8f2303
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08471005B2

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