Dimethylbarbituric acid → 4-(2-{4-[3-(tert-Butylamino-methyl)-phenyl]-pyrimidin-2-ylamino}-ethyl)-phenol

HRID 14911

Reaktionsgleichung

Reaktionsgleichung von HRID 14911
C(OC(=O)[N:6]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[N:15]=2)[CH:9]=1)C=C.C(N(C(C)C)CC)(C)C.CN1C(=O)CC(=O)N(C)C1=O>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:30]([NH:6][CH2:7][C:8]1[CH:9]=[C:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH2:21][CH2:22][C:23]3[CH:24]=[CH:25][C:26]([OH:29])=[CH:27][CH:28]=3)[N:15]=2)[CH:11]=[CH:12][CH:13]=1)([CH3:33])([CH3:31])[CH3:32]

Komponenten

6

Edukt 3

HCID 69860Dimethylbarbituric acidHCID 81531DiisopropylethylamineHCID 67045134tert-Butyl-(3-{2-[2-(4-hydroxy-phenyl)-ethylamino]-pyrimidin-4-yl}benzyl)-carbamic acid allyl ester2×

Produkt 1

HCID 586034084-(2-{4-[3-(tert-Butylamino-methyl)-phenyl]-pyrimidin-2-ylamino}-ethyl)-phenolAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

tert-Butyl-(3-{2-[2-(4-hydroxy-phenyl)-ethylamino]-pyrimidin-4-yl}benzyl)-carbamic acid allyl ester (intermediate 118, 176 mg) was dissolved in methylene chloride (5 mL), followed by addition of diisopropylethylamine (0.11 mL), 1,3-dimethylbarbituric acid (78 mg) then Pd(PPh3)4 (50 mg). The mixture was stirred at room temperature overnight. The mixture was washed with saturated NaHCO3, brine, dried over Na2SO4, filtered and chromatographed on silica gel with methylene chloride:methanol (95:5) to afford 112 mg of product in 78% yield. LC-MS showed the product had the expected M+H+ of 377. 1H NMR (Varian 300 MHz, CD3OD, shifts relative to the solvent peak at 3.31 ppm) δ 8.3 (d, 1H) 8.1 (s, 1H) 8.0 (d, 1H) 7.5 (m, 2H) 7.1 (m, 3H) 6.7 (m, 2H) 3.8 (s, 2H) 3.6 (m, 2H) 2.8 (m, 2H) 1.2 (s, 9H).

Aufarbeitung

  1. washThe mixture was washed with saturated NaHCO3, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customchromatographed on silica gel with methylene chloride:methanol (95:5)

Quellen und Nachweise

ORD-Eintrag
ord-0974be82a2404348a52ec87cf5a8e60b
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732444B2

Verknüpfte Notizen

Wird geladen…