Sodium hydride → 2-{6-[3(R)-Amino-piperidin-1-yl]-3-(3-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrile

HRID 505895

Reaktionsgleichung

Reaktionsgleichung von HRID 505895
Cl[C:2]1[N:7]([CH2:8][C:9]2[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=2[C:11]#[N:12])[C:6](=[O:17])[NH:5][C:4](=[O:18])[CH:3]=1.[H-].[Na+].[Li+].[Br-].[C:23]([C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH2:28]Br)#[N:24].Cl.Cl.[NH2:35][C@@H:36]1[CH2:41][CH2:40][CH2:39][NH:38][CH2:37]1.C(=O)(O)[O-].[Na+]>COCCOC.CN(C=O)C>[NH2:35][C@@H:36]1[CH2:41][CH2:40][CH2:39][N:38]([C:2]2[N:7]([CH2:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[C:11]#[N:12])[C:6](=[O:17])[N:5]([CH2:28][C:27]3[CH:30]=[CH:31][CH:32]=[C:25]([C:23]#[N:24])[CH:26]=3)[C:4](=[O:18])[CH:3]=2)[CH2:37]1

Komponenten

8

Edukt 6

HCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 97249Benzonitrile, 3-(bromomethyl)-HCID 516892Sodium BicarbonateHCID 113574682-((6-Chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)benzonitrileHCID 16211333(3R)-Piperidin-3-amine--hydrogen chloride (1/2)

Produkt 1

HCID 117750342-{6-[3(R)-Amino-piperidin-1-yl]-3-(3-cyano-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl}-benzonitrileAusbeute 84 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 18463208dimethoxyethane N,N-dimethylformamideLösungsmittel

Versuchsvorschrift

Compound 2 (65 mg, 0.25 mmol) in DME-DMF (2:1, 2.5 mL) was treated with 60% NaH (15 mg, 0.38 mmol) at 0° C. for 20 min, and then LiBr (25 mg) was added. 10 min later, m-cyano-benzyl bromide (55 mg, 0.28 mg) was added, and the mixture was stirred at RT for 5 h, and concentrated. The crude residue was dissolved in MeOH (3 mL). (R)-3-Amino-piperidine dihydrochloride (52 mg, 0.3 mmol) and sodium bicarbonate (100 mg) were added. The mixture was heated in a sealed tube at 120° C. for 2 h, and then filtered and concentrated. LC-MS purification gave the title compound 17 in 84% yield. 1H-NMR (400 MHz, CDCl3-CD3OD 10:1) δ 7.67 (d, J=7.8 Hz, 1H), 7.52-7.62 (m, 4H), 7.35-7.46 (m, 2H), 7.27 (d, J=7.8 Hz, 1H), 5.43 (s, 1H), 5.15-5.31 (ABq, J=40.9, 13.7 Hz, 2H), 5.04 (s, 2H), 3.40 (s, 1H), 3.40 (m 1H), 3.03 (m, 1H), 2.91 (m, 1H), 2.76 (s, 1H), 2.13 (s, 1H), 1.92 (m, 1H), 1.63-1.74 (m, 2H). MS (ES) [m+H] calc'd for C25H25N6O2, 441.2; found 441.2.

Aufarbeitung

  1. concentrationconcentrated
  2. dissolutionThe crude residue was dissolved in MeOH (3 mL)
  3. temperatureThe mixture was heated in a sealed tube at 120° C. for 2 h
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customLC-MS purification

Quellen und Nachweise

ORD-Eintrag
ord-17307f13b76c471d94f1a9fbd7c496ce
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07781584B2

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