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

HRID 419221

Reaktionsgleichung

Reaktionsgleichung von HRID 419221
Cl[C:2]1[CH:7]=[C:6]([O:8][CH:9]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:21])[N:3]=1.B([C:25]1[CH:36]=[CH:35][C:28]([CH2:29][C@@H:30]([C:32]([OH:34])=[O:33])[NH2:31])=[CH:27][CH:26]=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>[NH2:31][CH:30]([CH2:29][C:28]1[CH:35]=[CH:36][C:25]([C:2]2[CH:7]=[C:6]([O:8][CH:9]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([NH2:21])[N:3]=2)=[CH:26][CH:27]=1)[C:32]([OH:34])=[O:33]

Komponenten

7

Edukt 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 150315L-p-BoronophenylalanineHCID 866142944-Chloro-2-amino-6-[1-(4-methylphenyl)-2,2,2-trifluoro-ethoxy]-pyrimidine

Produkt 1

HCID 666494002-Amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(4-methylphenyl)-ethoxy]-pyrimidin-4-yl}-phenyl)-propionic acidAusbeute 32,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A microwave vial was charged with 4-chloro-2-amino-6-[1-(4-methylphenyl)-2,2,2-trifluoro-ethoxy]-pyrimidine (33 mg, 0.1 mmol), 4-borono-L-phenylalanine (31 mg, 0.15 mmol) and 1 ml of acetonitrile, 0.7 ml of water. Aqueous sodium carbonate (0.3 ml, 1N) was added to above solution followed by 5 mol percent of dichlorobis(triphenylphosphine)-palladium(II). The reaction vessel was sealed and heated to 150° C. for 5 minutes with microwave. After cooling, the reaction mixture was evaporated to dryness. The residue was dissolved in 2.5 ml of methanol, was then purified by Prep-LC to give 14.6 mg of 2-amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(4-methylphenyl)-ethoxy]-pyrimidin-4-yl}-phenyl)-propionic acid. 1H NMR (300 MHz, CD3OD) δ 7.94 (d, J=8.20 Hz, 2H), 7.47 (d, J=7.24 Hz, 4 H), 7.27 (d, J=8.01 Hz, 2H) 6.80 (s, 1H), 6.75 (m, 1H), 4.30 (t, 1 H), 3.21-3.44 (m, 2 H), 2.37 (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 then purified by Prep-LC

Quellen und Nachweise

ORD-Eintrag
ord-ba22e5e7cc4b4b52a7afce4b32a97511
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093291B2

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