Thiourea → HCID 59790146, Verbindung

HRID 1963733Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1963733
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N:12]=[C:13]=S.[NH2:15][C:16]1[CH:17]=[C:18]([CH:37]=[CH:38][C:39]=1[NH:40][CH3:41])[O:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:36])[CH2:28][N:29]2[CH2:33][CH2:32][CH2:31][CH:30]2[CH2:34][OH:35])[CH:21]=1.NC(N)=S>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]1[N:40]([CH3:41])[C:39]2[CH:38]=[CH:37][C:18]([O:19][C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:36])[CH2:28][N:29]4[CH2:33][CH2:32][CH2:31][C@H:30]4[CH2:34][OH:35])[CH:21]=3)=[CH:17][C:16]=2[N:15]=1

Komponenten

5

Edukt 3

HCID 2723790ThioureaHCID 34078242-Fluoro-5-(trifluoromethyl)phenyl isothiocyanateHCID 69008962N-[4-(3-Amino-4-methylamino-phenoxy)-pyridin-2-yl]-2-(2-hydroxymethyl-pyrrolidin-1-yl)-acetamide

Produkt 1

HCID 59790146HCID 59790146, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

2-Fluoro-5-(trifluoromethyl)phenyl isothiocyanate was added to a solution of N-[4-(3-Amino-4-methylamino-phenoxy)-pyridin-2-yl]-2-(2-hydroxymethyl-pyrrolidin-1-yl)-acetamide in methanol. Reaction was stirred at room temperature for 15 hours. Thiourea formation was confirmed by LC/MS. Ferric chloride was added and the resulting mixture was stirred at room temperature for 4 hours. After cyclization was complete by LC/MS the reaction mixture was concentrated and aqueous sodium carbonate was added until basic pH. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water then brine, and dried over magnesium sulfate and concentrated. The crude product was purified by reverse phase HPLC. MS: MH+=559.3.

Aufarbeitung

  1. customReaction
  2. stirringthe resulting mixture was stirred at room temperature for 4 hours
  3. concentrationwas concentrated
  4. additionaqueous sodium carbonate was added until basic pH
  5. customThe reaction mixture was partitioned between ethyl acetate and water
  6. washThe organic layer was washed with water
  7. dry with materialbrine, and dried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe crude product was purified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-4897f81dc2f84791b2b061568b328181
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415382B2

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