1-Pyrrolidineethanamine → Toceranib

HRID 271545Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 271545
[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].CN(C)C=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:55][CH2:56][CH2:57][N:58]1[CH2:62][CH2:61][CH2:60][CH2:59]1>C(N(CC)CC)C>[N:58]1([CH2:57][CH2:56][NH:55][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])[CH2:62][CH2:61][CH2:60][CH2:59]1

Komponenten

6

Edukt 4

HCID 13441-PyrrolidineethanamineHCID 6228DimethylformamideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 10979489Sunitinib acid

Produkt 1

HCID 5329106ToceranibAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

5-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (100 g) and dimethylformamide (500 mL) were stirred and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (221 g), 1-(2-aminoethyl)pyrrolidine (45.6 g) and triethylamine (93 mL) were added. The mixture was stirred for 2 hours at ambient temperature. The solid product was collected by vacuum filtration and washed with ethanol. The solids were slurry-washed by stirring in ethanol (500 mL) for one hour at 64° C. and cooled to room temperature. The solids were collected by vacuum filtration, washed with ethanol, and dried under vacuum to give 5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide (101.5 g, 77% yield). 1H-NMR (dimethylsulfoxide-d6) δ 1.60 (m, 4H, 2×CH2), 2.40, 2.44 (2×s, 6H, 2×CH3), 2.50 (m, 4H, 2×CH2), 2.57, 3.35 (2×m, 4H, 2×CH2), 7.53, 7.70, 7.73, 7.76 (4×m, 4H, aromatic and vinyl), 10.88 (s, 1H, CONH), 13.67 (s, 1H, pyrrole NH). MS m/z 396 [M+1].

Aufarbeitung

  1. filtrationThe solid product was collected by vacuum filtration
  2. washwashed with ethanol
  3. washThe solids were slurry-washed
  4. stirringby stirring in ethanol (500 mL) for one hour at 64° C.
  5. temperaturecooled to room temperature
  6. filtrationThe solids were collected by vacuum filtration
  7. washwashed with ethanol
  8. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-dd34a27aeb6a40f2bb0db64c4cbe6124
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07452913B2

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