Ethyl Acetate → 4-(1-(5-Cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazine-3-carbonitrile

HRID 386556Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 386556
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([N:10]2[C:15](=[O:16])[CH:14]=[C:13]([O:17][CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[C:12]([C:24]#[N:25])=[N:11]2)[CH:6]=[CH:7][C:8]=1[Cl:9].CCN(C(C)C)C(C)C.Cl[C:36]1[N:41]=[CH:40][C:39]([CH:42]2[CH2:44][CH2:43]2)=[CH:38][N:37]=1.CCOC(C)=O>CN1C(=O)CCC1>[CH:42]1([C:39]2[CH:38]=[N:37][C:36]([N:21]3[CH2:20][CH2:19][CH:18]([O:17][C:13]4[C:12]([C:24]#[N:25])=[N:11][N:10]([C:5]5[CH:6]=[CH:7][C:8]([Cl:9])=[C:3]([Cl:2])[CH:4]=5)[C:15](=[O:16])[CH:14]=4)[CH2:23][CH2:22]3)=[N:41][CH:40]=2)[CH2:44][CH2:43]1

Komponenten

6

Edukt 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 468640872-Chloro-5-cyclopropylpyrimidineHCID 674465361-(3,4-dichlorophenyl)-6-oxo-4-(piperidin-4-yloxy)-1,6-dihydropyridazine-3-carbonitrile HCl

Produkt 1

HCID 446216584-(1-(5-Cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazine-3-carbonitrileAusbeute 40,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a stirring solution of 1-(3,4-dichlorophenyl)-6-oxo-4-(piperidin-4-yloxy)-1,6-dihydropyridazine-3-carbonitrile HCl (50 mg, 0.137 mmol) in NMP (2 mL) at room temperature under argon was added DIPEA (53.1 mg, 0.411 mmol) and 2-chloro-5-cyclopropylpyrimidine (31.7 mg, 0.205 mmol). The resulting reaction mixture was heated at 100° C. under argon overnight. 15 mL of EtOAc was added to the reaction mixture. The reaction mixture was washed with water (15 mL), and brine (15 mL). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM (˜2 ml) and loaded onto a 40 g ISCO silica gel column which was eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes. 27 mg (38.8%) of 4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazine-3-carbonitrile was obtained as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 0.50-0.66 (m, 2H) 0.82-0.98 (m, 2H) 1.64-1.79 (m, 1H) 1.83-1.99 (m, 2H) 1.99-2.16 (m, 2H) 3.60-3.90 (m, 2H) 3.96-4.25 (m, 2H) 4.56-4.87 (m, 1H) 6.31 (s, 1H) 7.41-7.50 (m, 1H) 7.50-7.60 (m, 1H) 7.73 (d, J=2.20 Hz, 1H) 8.05-8.18 (m, 2H). MS (ESI) 483 (M+H).

Aufarbeitung

  1. customThe resulting reaction mixture
  2. washThe reaction mixture was washed with water (15 mL), and brine (15 mL)
  3. dry with materialOrganic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in a small amount of DCM (˜2 ml)
  7. washwas eluted with a 20 min gradient from 20% to 100% EtOAc/Hexanes

Quellen und Nachweise

ORD-Eintrag
ord-c2592222cad144cf9a1b7e0b46052c98
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08372837B2

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