Diisopropylethylamine → 2-(4-{4-[7-(3-tert-Butylsulfamoylphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxyphenyl)piperidin-1-yl)-acetamide

HRID 1262114

Reaktionsgleichung

Reaktionsgleichung von HRID 1262114
[C:1]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:23]3[C:18]([CH:19]=[N:20][C:21](O)=[N:22]3)=[CH:17][CH:16]=2)[CH:10]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[N-](S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O.[NH2:49][C:50]1[CH:55]=[CH:54][C:53]([CH:56]2[CH2:61][CH2:60][N:59]([CH2:62][C:63]([NH2:65])=[O:64])[CH2:58][CH2:57]2)=[CH:52][C:51]=1[O:66][CH3:67]>CN(C=O)C>[C:1]([NH:5][S:6]([C:9]1[CH:10]=[C:11]([C:15]2[N:23]3[C:18]([CH:19]=[N:20][C:21]([NH:49][C:50]4[CH:55]=[CH:54][C:53]([CH:56]5[CH2:61][CH2:60][N:59]([CH2:62][C:63]([NH2:65])=[O:64])[CH2:58][CH2:57]5)=[CH:52][C:51]=4[O:66][CH3:67])=[N:22]3)=[CH:17][CH:16]=2)[CH:12]=[CH:13][CH:14]=1)(=[O:7])=[O:8])([CH3:3])([CH3:2])[CH3:4]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 4176748N-Propyl-Methyl Piperidinium Bis(trifluoroMethylsulfonyl)ImideHCID 569459622-[4-(4-Amino-3-methoxy-phenyl)-piperidin-1-yl]-acetamideHCID 178449976HCID 178449976, Verbindung

Produkt 1

HCID 667120542-(4-{4-[7-(3-tert-Butylsulfamoylphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxyphenyl)piperidin-1-yl)-acetamideAusbeute 11,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

In a 10 mL sealed tube, to N-tert-Butyl-3-(2-hydroxy-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzenesulfonamide (127.4 mg, 0.368 mmol) and N,N-Diisopropylethylamine (0.257 mL, 1.47 mmol) in 3.2 mL of anhydrous DMF was added N-Phenylbis(trifluoromethane-sulfonimide (113 mg, 0.318 mmol). After stirring at room temperature for 1 hour, 2-[4-(4-Amino-3-methoxy-phenyl)-piperidin-1-yl]-acetamide (92 mg, 0.349 mmol) was added. The reaction mixture was heated at 65° C. overnight. The reaction was conc. in vacuo. The reaction mixture was purified via silica gel column chromatography using DCM then 500:15:10 DCM:MeOH:7N NH3/MeOH as the eluant. The collected fractions afforded 2-(4-{4-[7-(3-tert-Butylsulfamoylphenyl)pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-3-methoxyphenyl)piperidin-1-yl)-acetamide as a yellow solid (23.0 mg, 11%). MP 250-252° C. LCMS (E/I+) 592.25 (M+H). 1H NMR (DMSO-d6)-9.02 (s, 1H), 8.55 (s, 1H), 8.37 (d, 1H, J=7.84 Hz), 7.99 (d, 1H, J=7.96 Hz), 7.85 (s, 1H), 7.83 (s, 1H), 7.69 (t, 1H, J=7.86 Hz), 7.63 (s, 1H), 7.23 (d, 1H, J=4.80 Hz), 7.21 (br s, 1H), 7.15 (br s, 1H), 7.01 (d, 1H, J=4.72 Hz), 6.95 (s, 1H), 6.92 (s, 1H), 3.88 (s, 3H), 2.97-2.90 (m, 2H), 2.88 (s, 2H), 2.49-2.41 (m, 1H), 2.22-2.11 (m, 2H), 1.84-1.72 (m, 4H), 1.12 (s, 9H).

Aufarbeitung

  1. customIn a 10 mL sealed tube
  2. temperatureThe reaction mixture was heated at 65° C. overnight
  3. customThe reaction mixture was purified via silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-f946b20d7f6c4df399835fe3f46f65cf
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08471005B2

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