p-Toluenesulfonic acid monohydrate → 2-(4-(4-Hydroxypiperidin-1-yl)phenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one

HRID 591597Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 591597
[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[OH:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=2)[CH2:18][CH2:17]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.S(=O)(O)[O-].[Na+]>CN(C)C(=O)C>[OH:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:29]=[CH:28][C:25]([C:26]3[NH:6][C:4](=[O:5])[C:3]4[C:7]([O:13][CH3:14])=[CH:8][C:9]([O:11][CH3:12])=[N:10][C:2]=4[N:1]=3)=[CH:24][CH:23]=2)[CH2:18][CH2:17]1

Komponenten

6

Edukt 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 127174464-(4-Hydroxypiperidin-1-yl)benzaldehydeHCID 23665763Sodium BisulfiteHCID 666066902-Amino-4,6-dimethoxy-nicotinamide

Produkt 1

HCID 1359390862-(4-(4-Hydroxypiperidin-1-yl)phenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
135 °C

Versuchsvorschrift

A mixture of 2-amino-4,6-dimethoxy-nicotinamide (0.60 g, 3.0 mmol), 4-(4-hydroxy-piperidin-1-yl)-benzaldehyde (0.81 g, 3.9 mmol), p-toluenesulfonic acid monohydrate (1.25 g, 6.6 mmol) and sodium bisulfite (1.06 g, 6.0 mmol) in N,N-dimethylacetamide (8.0 mL) was stirred at 135° C. under N2 for 16 hours and then cooled to room temperature. The mixture was concentrated to dryness under reduced pressure. Water (40 mL) was added to the residue and stirred for 0.5 hours. The precipitate was filtered and the solid was rinsed with water and air-dried. The crude solid was purified by column chromatography (silica gel 230-400 mesh; eluting with 4% methanol in dichloromethane) to afford the title compound, as a yellow solid. Yield: 0.29 g (25.2%). MP 284-286° C. 1H NMR (400 MHz, DMSO-d6): δ 12.09 (s, 1H), 8.12 (d, J=8.8 Hz, 2H), 7.02 (d, J=8.8 Hz, 2H), 6.32 (s, 1H), 4.73 (d, J=4.4 Hz, 1H), 3.94 (s, 3H), 3.89 (s, 3H), 3.72 (m, 3H), 3.05 (m, 2H), 1.80 (m, 2H), 1.43 (m, 2H). MS (ES+) m/z: 383.06 (M+1).

Aufarbeitung

  1. temperaturecooled to room temperature
  2. concentrationThe mixture was concentrated to dryness under reduced pressure
  3. additionWater (40 mL) was added to the residue
  4. stirringstirred for 0.5 hours
  5. filtrationThe precipitate was filtered
  6. washthe solid was rinsed with water
  7. customair-dried
  8. customThe crude solid was purified by column chromatography (silica gel 230-400 mesh; eluting with 4% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-6222928783b64f1bbad32ddeca70e0a6
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238640B2

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