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

HRID 1262327

Reaktionsgleichung

Reaktionsgleichung von HRID 1262327
O[C:2]1[N:7]=[CH:6][C:5]2=[C:8]([CH3:23])[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.C(N(CC)C(C)C)(C)C.C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.[NH2:54][C:55]1[CH:60]=[CH:59][C:58]([CH:61]2[CH2:66][CH2:65][N:64]([CH2:67][C:68]([NH2:70])=[O:69])[CH2:63][CH2:62]2)=[CH:57][C:56]=1[O:71][CH3:72]>CN(C)C=O>[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:54][C:55]3[CH:60]=[CH:59][C:58]([CH:61]4[CH2:66][CH2:65][N:64]([CH2:67][C:68]([NH2:70])=[O:69])[CH2:63][CH2:62]4)=[CH:57][C:56]=3[O:71][CH3:72])=[N:3]2)=[C:8]([CH3:23])[CH:9]=1)(=[O:20])=[O:19]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 142176Phenyl triflimideHCID 569459622-[4-(4-Amino-3-methoxy-phenyl)-piperidin-1-yl]-acetamideHCID 178422626HCID 178422626, Verbindung

Produkt 1

HCID 569458462-[4-(4-{7-[2-(Methanesulfonyl-methyl-amino)-phenyl]-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidin-1-yl]-acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Into an 8-dram vial, N-[2-(2-Hydroxy-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide (87 mg, 0.26 mmol), N,N-Dimethylformamide (0.948 mL), N,N-Diisopropylethylamine (0.100 mL, 0.576 mmol), and N-Phenylbis(trifluoromethanesulphonimide) (0.112 g, 0.314 mmol) were added. The reaction was stirred at room temperature for 30 minutes. 2-[4-(4-Amino-3-methoxy-phenyl)-piperidin-1-yl]-acetamide (0.152 g, 0.576 mmol) was then added. The reaction mixture was heated at 120° C. for 4 hours. The solvent was removed under vacuum overnight. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were lyophilized to give a yellow solid. The solid was partitioned with NaHCO3 and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum to give 2-[4-(4-{7-[2-(Methanesulfonyl-methyl-amino)-phenyl]-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino}-3-methoxy-phenyl)-piperidin-1-yl]-acetamide as a yellow solid. LCMS (E/I+) 578.16 (M+H). NMR 1H (DMSO-d6)-8.95 (s, 1H), 7.93-7.98 (m, 1H), 7.88 (d, 1H, J=8.18 Hz), 7.61-7.67 (m, 1H), 7.57 (s, 1H), 7.51-7.56 (m, 1H), 7.21 (s, 1H), 7.14 (s, 1H), 6.89 (s, 1H), 6.81 (s, 1H), 6.68 (d, 1H, J=8.51 Hz), 3.84 (s, 3H), 3.05 (s, 3H), 2.85-2.95 (m, 7H), 2.35-2.45 (m, 4H), 2.08-2.28 (m, 2H), 1.64-1.81 (m, 4H).

Aufarbeitung

  1. temperatureThe reaction mixture was heated at 120° C. for 4 hours
  2. customThe solvent was removed under vacuum overnight
  3. customThe reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN
  4. customto give a yellow solid
  5. customThe solid was partitioned with NaHCO3 and DCM
  6. customThe organic was separated
  7. washwashed with Brine
  8. dry with materialdried over Na2SO4
  9. filtrationThe solid was filtered
  10. washwashed with DCM
  11. customThe solvent was removed under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-ae166c04266041dbacb691441b5722ec
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08471005B2

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