Potassium Phosphate, Tribasic → 1-(2-Amino-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-5-yl)-4-methylpiperazin-2-one

HRID 706444Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 706444
I[C:2]1[CH:30]=[CH:29][C:5]2[N:6]([CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]4[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=4)=[C:13]([O:27][CH3:28])[CH:12]=3)[C:7]([NH2:9])=[N:8][C:4]=2[CH:3]=1.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][C:34](=[O:38])[CH2:33]1.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I>[NH2:9][C:7]1[N:6]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)=[C:13]([O:27][CH3:28])[CH:12]=2)[C:5]2[CH:4]=[CH:3][C:2]([N:35]3[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][C:34]3=[O:38])=[CH:30][C:29]=2[N:8]=1

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 137042831-Methyl-3-oxopiperazineHCID 1181140555-iodo-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-2-amine

Produkt 1

HCID 1180097861-(2-Amino-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-5-yl)-4-methylpiperazin-2-oneAusbeute 12,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
145 °C

Versuchsvorschrift

To a stirred suspension of 5-iodo-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazol-2-amine (0.25 g, 0.48 mmol) in 1,4-dioxane (8 mL) was added 4-methylpiperazin-2-one (0.11 g, 0.96 mmol), CuI (0.036 mg, 0.19 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (0.044 g, 0.38 mmol), and tribasic potassium phosphate (0.32 g, 1.52 mmol). The mixture was heated to 145° C. in a microwave reactor. After 3 h, the mixture was allowed to cool to room temperature and was filtrated through Celite. The filtrate was concentrated, and the residue was purified by silica gel chromatography (2-5% methanol/dichloromethane elute) followed by prep-HPLC to afford 0.030 g (12%) of the product as a white solid: 1H NMR (500 MHz, CDCl3) δ 8.17 (s, 1H), 7.66 (dd, J=8.0, 2.0 Hz, 1H), 7.25 (s, 1H), 7.01 (d, J=8.0 Hz, 1H), 6.86 (d, J=8.0 Hz, 1H), 6.79 (d, J=8.0 Hz, 1H), 6.76-6.74 (m, 2H), 6.64 (d, J=7.5 Hz, 1H), 4.99 (s, 2H), 4.89 (br s, 2H), 4.81 (s, 2H), 3.94 (s, 3H), 3.79 (s, 3H), 3.72 (t, J=5.0 Hz, 2H), 3.30 (s, 2H), 2.82 (t, J=5.0 Hz, 2H), 2.44 (s, 3H) ppm; (M+1)=503.

Aufarbeitung

  1. temperatureto cool to room temperature
  2. filtrationwas filtrated through Celite
  3. concentrationThe filtrate was concentrated
  4. customthe residue was purified by silica gel chromatography (2-5% methanol/dichloromethane elute)

Quellen und Nachweise

ORD-Eintrag
ord-06eb22b6dac149a48f91b4f94a44cc63
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09174986B2

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