Methylamine → Ethyl 1-(methylamino)isoquinoline-7-carboxylate

HRID 880975Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 880975
CN.O1CCCC1.Cl[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:17]=2)[CH:12]=[CH:11][N:10]=1.COC1C=CC([CH2:30][NH:31]C2C3C(=CC=C(C(O)=O)C=3)C=CN=2)=CC=1>>[CH3:30][NH:31][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:17]=2)[CH:12]=[CH:11][N:10]=1

Komponenten

5

Edukt 4

HCID 6329Methylamine2×HCID 8028TetrahydrofuranHCID 674916931-(4-Methoxybenzylamino)isoquinoline-7-carboxylic acidHCID 86664617Ethyl 1-chloroisoquinoline-7-carboxylate

Produkt 1

HCID 67491404Ethyl 1-(methylamino)isoquinoline-7-carboxylateAusbeute 85 %

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A solution of methylamine in tetrahydrofuran (30 mL, 60 mmol, 2 M) was added to ethyl 1-chloroisoquinoline-7-carboxylate (formed in Step 3 of Intermediate 27) (705 mg, 2.99 mmol) in a sealed tube. The reaction was heated to 60° C. and stirred overnight. LCMS indicated the reaction was not complete. Additional methylamine (10 mL, 20 mmol, 2 M in THF) was added and the reaction was heated to 60° C. for another 18 hours. The reaction was cooled to room temperature and concentrated. The residue was partitioned between water and dichloromethane. The organic layer was dried over magnesium sulphate, filtered, and concentrated. Purification by flash column chromatography (25-65% ethyl acetate/heptanes) gave the title compound (584 mg, 85%) as a yellow oil that solidified upon standing. +ESI (M+H) 231.1; 1H NMR (400 MHz, DMSO-d6, δ): 8.83-8.94 (m, 1H), 8.07 (dd, J=8.58, 1.56 Hz, 1H), 7.99 (d, J=5.85 Hz, 1H), 7.89 (d, J=4.49 Hz, 1H), 7.77 (d, J=8.58 Hz, 1H), 6.92 (d, J=5.07 Hz, 1H), 4.38 (q, J=7.02 Hz, 2H), 2.97 (d, J=4.49 Hz, 3H), 1.38 (t, J=7.12 Hz, 3H).

Aufarbeitung

  1. temperaturethe reaction was heated to 60° C. for another 18 hours
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated
  4. customThe residue was partitioned between water and dichloromethane
  5. dry with materialThe organic layer was dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash column chromatography (25-65% ethyl acetate/heptanes)

Quellen und Nachweise

ORD-Eintrag
ord-84cec0cd5590481687db87a8606afd11
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08993586B2

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