Triethylamine → (z)-n-(2-Aminophenyl)-6-(2-(2-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-3,5-dimethyl-1h-pyrrole-4-carboxamido)ethylamino)nicotinamide

HRID 1695030Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1695030
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])/[C:5]/2=[CH:12]\[C:13]1[NH:17][C:16]([CH3:18])=[C:15]([C:19]([OH:21])=O)[C:14]=1[CH3:22].Cl.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C.[NH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[NH:59][C:60](=[O:71])[C:61]1[CH:66]=[CH:65][C:64]([NH:67][CH2:68][CH2:69][NH2:70])=[N:63][CH:62]=1>[Cl-].[Na+].O.CN(C=O)C>[NH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[NH:59][C:60](=[O:71])[C:61]1[CH:66]=[CH:65][C:64]([NH:67][CH2:68][CH2:69][NH:70][C:19]([C:15]2[C:14]([CH3:22])=[C:13](/[CH:12]=[C:5]3\[C:6](=[O:11])[NH:7][C:8]4[C:4]\3=[CH:3][C:2]([F:1])=[CH:10][CH:9]=4)[NH:17][C:16]=2[CH3:18])=[O:21])=[N:63][CH:62]=1

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10979489Sunitinib acidHCID 57993739N-(2-aminophenyl)-6-(2-aminoethylamino)nicotinamideHCID 178418300HCID 178418300, Verbindung

Produkt 1

HCID 44538256(z)-n-(2-Aminophenyl)-6-(2-(2-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-3,5-dimethyl-1h-pyrrole-4-carboxamido)ethylamino)nicotinamideAusbeute 89,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

5-(5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (300 mg, 1 mmol) and 8 ml of DMF were stirred at room temperature while 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (384 mg, 2 mmol), hydroxybenzotriazole (162 mg, 1.2 mmol), triethylamine (404 mg, 4 mmol) and N-(2-aminophenyl)-6-(2-aminoethylamino)nicotinamide (284 mg, 1.05 mmol) were added. The mixture was stirred for 20 hours at room temperature. The mixture was diluted with 400 mL of brine. The solids were collected by vacuum filtration, washed with water and dried under vacuum to give the title compound (493 mg, 89%) as a yellow solid. 1H NMR (DMSO-d6)δ2.41 (s, 3H, pyrrole-CH3), 2.43 (s, 3H, pyrrole-CH3), 3.43 (m, 2H, CH2), 3.48 (m, 2H, CH2), 4.86 (s, 2H, benzene-NH2), 6.56 (m, 2H), 6.76 (d, J=8.0 Hz, 1H), 6.84 (m, 1H), 6.92 (m, 2H), 7.12 (d, J=8.0 Hz, 1H), 7.26 (s 1H), 7.71˜7.77 (m, 3H), 7.94 (d,J=8.0 Hz, 1H), 8.65 (s, 1H), 9.38 (s, 1H, benzene-NH), 10.90 (s, 1H, indolinone-NH), 13.69 (s, 1H, pyrrole-NH). LC-MS (m/z) 554 (M+1).

Aufarbeitung

  1. additionwere added
  2. filtrationThe solids were collected by vacuum filtration
  3. washwashed with water
  4. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-30022517f00f4440b48f647db090c7b0
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08158656B2

Notizen zur Reaktion

Wird geladen…