Acetonitrile → (S)-2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl)-propionic acid

HRID 1988010

Reaktionsgleichung

Reaktionsgleichung von HRID 1988010
Cl[C:2]1[CH:7]=[C:6]([O:8][CH:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]2[C:24]([CH3:25])=[CH:23][S:22][CH:21]=2)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:26])[N:3]=1.B([C:30]1[CH:41]=[CH:40][C:33]([CH2:34][C@@H:35]([C:37]([OH:39])=[O:38])[NH2:36])=[CH:32][CH:31]=1)(O)O.C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:36][C@@H:35]([CH2:34][C:33]1[CH:40]=[CH:41][C:30]([C:2]2[CH:7]=[C:6]([O:8][CH:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]3[C:24]([CH3:25])=[CH:23][S:22][CH:21]=3)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:26])[N:3]=2)=[CH:31][CH:32]=1)[C:37]([OH:39])=[O:38]

Komponenten

7

Edukt 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 150315L-p-BoronophenylalanineHCID 866210844-Chloro-6-{2,2,2-trifluoro-1-[2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-2-ylamine

Produkt 1

HCID 25025099(S)-2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-4-yl)-phenyl)-propionic acidAusbeute 38,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

In a microwave vial, 4-chloro-6-{2,2,2-trifluoro-1-[2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-2-ylamine (30 mg, 0.075 mmol), 4-borono-L-phenylalanine (19 mg, 0.09 mmol), 1 ml of actonitrile and 0.7 ml of water were mixed. 0.3 ml of 1N aqueous sodium carbonate was added to mixture, followed by 5 mole percent of dichlorobis-(triphenylphosphine)-palladium(II). The reaction vessel was sealed and heated at 150° C. for 5 minutes with microwave irradiation. After cooling, the reaction mixture was evaporated to dryness. The residue was dissolved in 2.5 ml of methanol, and then was purified by Prep HPLC to give 15.1 mg of (S)-2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(2-(4-methyl-thiophen-3-yl)-phenyl]-ethoxy}-pyrimidin-4-yl}-phenyl)-propionic acid. 1H NMR (400 MHz, CD3OD) δ (ppm) 7.94 (d, J=8 Hz, 2H), 7.80 (s, 1H), 7.50 (m, 5H), 7.25 (m, 2H), 7.03 (s, 1H), 6.94 (s, 1H), 4.31 (t, J=5.6, 1H), 3.48 (m, 1H), 3.26 (m, 1H), 1.98 (s, 3H).

Aufarbeitung

  1. customThe reaction vessel was sealed
  2. temperatureAfter cooling
  3. customthe reaction mixture was evaporated to dryness
  4. dissolutionThe residue was dissolved in 2.5 ml of methanol
  5. customwas purified by Prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-503827162e2445e1b5bc8feb4a388181
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07553840B2

Verknüpfte Notizen

Wird geladen…