Dimethylformamide → N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-4-methylpiperazine-1-carboxamide

HRID 1502272Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1502272
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:31])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19](=O)[O:20]C4C=CC([N+]([O-])=O)=CC=4)[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1.CN(C)C=O.[CH3:37][N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:31])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH:18][C:19]([N:41]4[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]4)=[O:20])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1

Komponenten

5

Edukt 3

HCID 6228DimethylformamideHCID 531671-MethylpiperazineHCID 679748684-Nitrophenyl 7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylcarbamate

Produkt 1

HCID 67974856N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-4-methylpiperazine-1-carboxamideAusbeute 4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

4-nitrophenyl 7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylcarbamate (0.156 g, 0.374 mmol) was dissolved in N,N-dimethylformamide (2.0 mL, 26 mmol) and 1-methyl-piperazine (0.20 mL, 1.8 mmol) was added. The reaction mixture was heated at 90° C. for 1 hour. The reaction mixture was then diluted with dichloromethane, washed with saturated aqueous NaHCO3, dried over MgSO4, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-20% methanol in dichloromethane with 2% triethylamine) followed by reverse phase HPLC and lyophilization to yield 5.4 mg (4%) of N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-4-methylpiperazine-1-carboxamide. LCMS (ESI): RT (min)=4.017, M+H=379.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 9.12 (s, 1H), 8.23 (s, 1H), 7.99 (s, 1H), 7.88 (d, J=8.3 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 7.38 (s, 1H), 7.16 (t, J=8.3 Hz, 2H), 3.52 (s, 4H), 2.33 (s, 4H), 2.25 (s, 3H), 2.21 (s, 3H).

Aufarbeitung

  1. washwashed with saturated aqueous NaHCO3
  2. dry with materialdried over MgSO4
  3. customevaporated in vacuo
  4. customThe crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-20% methanol in dichloromethane with 2% triethylamine)

Quellen und Nachweise

ORD-Eintrag
ord-e978de33fa144fada63bc7d64f721981
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206175B2

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