N,N-Dimethylglycine → 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60448

Reaktionsgleichung

Reaktionsgleichung von HRID 60448
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[C:15](Br)[CH:16]=[N:17][C:10]=2[N:9]([CH3:27])[C:8]1=[O:28])=O.CN(C)CC(O)=O.C([O-])([O-])=O.[Cs+].[Cs+].[F:42][C:43]([F:53])([F:52])[O:44][C:45]1[CH:46]=[C:47]([OH:51])[CH:48]=[CH:49][CH:50]=1>O1CCOCC1.CC(=O)OCC.O.[Cu]I>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][C:14]2[C:11]3[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:28])[N:9]([CH3:27])[C:10]=3[N:17]=[CH:16][C:15]=2[O:51][C:47]2[CH:48]=[CH:49][CH:50]=[C:45]([O:44][C:43]([F:42])([F:52])[F:53])[CH:46]=2)=[CH:25][CH:24]=1

Komponenten

9

Edukt 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 27332613-(Trifluoromethoxy)phenolHCID 1188758893-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

Produkt 1

HCID 1188755345-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneAusbeute 15,2 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a mixture of 3-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (40 mg, 0.086 mmol), N,N-dimethylglycine (4.4 mg, 0.043 mmol), CuI (2.0 mg, 0.011 mmol), and Cs2CO3 (56 mg, 0.172 mmol) in dioxane (1 mL) was added 3-(trifluoromethoxy)phenol (23 mg, 0.130 mmol). The reaction was heated at 120° C. (MW) for 2 h, cooled to RT then diluted with EA (15 mL) and water (10 mL). The organic layer was washed with water (10 mL) and brine (10 mL), dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (7 mg, 15% yield) as a white solid. 1H NMR (CDCl3) δ: 8.36 (s, 1H), 7.32 (t, J=8.3 Hz, 1H), 7.16 (s, 4H), 6.98 (d, J=8.3 Hz, 1H), 6.75 (dd, J=13.0, 4.7 Hz, 2H), 4.71 (s, 2H), 4.24 (t, J=6.1 Hz, 2H), 3.72 (s, 3H), 3.55 (t, J=5.5 Hz, 2H), 1.98-1.87 (m, 2H). LCMS: MH+ 536 and TR=3.320 min.

Aufarbeitung

  1. temperatureThe reaction was heated at 120° C. (MW) for 2 h
  2. washThe organic layer was washed with water (10 mL) and brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by Prep HPLC

Quellen und Nachweise

ORD-Eintrag
ord-0cdeae10d7854a9a97eef2a442af17c3
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440972B2

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