Chlorosuccinimide → 4-chloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine

HRID 597943Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 597943
[CH3:1][O:2][C:3]1[C:4]([NH2:21])=[CH:5][C:6]2[CH:12]([CH3:13])[CH2:11][N:10]([C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[CH2:9][CH2:8][C:7]=2[N:20]=1.C1C(=O)N([Cl:29])C(=O)C1>CC#N>[Cl:29][C:5]1[C:6]2[CH:12]([CH3:13])[CH2:11][N:10]([C:14](=[O:19])[C:15]([F:18])([F:16])[F:17])[CH2:9][CH2:8][C:7]=2[N:20]=[C:3]([O:2][CH3:1])[C:4]=1[NH2:21]

Komponenten

4

Edukt 2

HCID 31398ChlorosuccinimideHCID 23654286HCID 23654286, Verbindung

Produkt 1

HCID 236543764-chloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amineAusbeute 49 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of 2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (303 mg, 1.00 mmol) in MeCN (6 ml) was added a solution of NCS (134 mg, 1.00 mmol) in MeCN (6 ml). The resulting mixture was stirred for 2 h at 50° C. and then quenched with excess of sat. aq. NaHCO3 and extracted with EtOAc. The organic layer was dried over Na2SO4, concentrated in vacuo and purified by column chromatography to give 165 mg (49%) of 4-chloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine. 1H-NMR (CDCl3) δ 4.28 (0.5H), 3.95 (2.5H), 3.88 (3H), 3.71 (2H), 3.61 (1H), 3.34 (1H), 3.16 (1H), 2.99 (1H), 1.13 (3H) ppm. To a solution of CuBr2 (43.0 mg, 0.19 mmol) and nBuNO2 (28.0 μl, 0.24 mmol) in MeCN (2.7 ml) was added a solution of 4-chloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-3-amine (54.0 mg, 0.16 mmol) in MeCN (2 ml) at room temperature. After leaving the mixture for 16 h at room temperature, it was heated at 50° C. for 4 h. After removal of MeCN under reduced pressure, the reaction was quenched with sat. aq. NaHCO3 and extracted with EtOAc. The organic layer was dried over Na2SO4, concentrated in vacuo and purified by column chromatography to give 45 mg (70%) of 3-bromo-4-chloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H NMR (CDCl3) δ 4.29 (0.5H), 4.00 (0.5H), 3.90 (3H), 3.85 (1H), 3.75 (1H), 3.40 (1H), 3.30 (1H), 3.20 (1H), 3.10 (1H), 1.16 (3H) ppm. A mixture of 3-bromo-4-chloro-2-methoxy-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (60 mg, 0.15 mmol), K2CO3 (62 mg, 0.45 mmol), MeOH (2.4 ml) and H2O (0.5 ml) was heated at 55-60° C. for 1 h. After removal of solvent under reduced pressure, the mixture was taken into aq. NaHCO3 and extracted with EtOAc. The organic layer was dried and concentrated in vacuo to give 45 mg (98%) of 3-bromo-4-chloro-2-methoxy-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 3.89 (s, 3H), 3.58 (m, 1H), 3.22 (m, 2H), 3.09 (dd, 1H), 2.93 (m, 2H), 2.71 (dd, 1H), 1.24 (d, 3H) ppm.

Aufarbeitung

  1. customquenched with excess of sat. aq. NaHCO3
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. custompurified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-d26464dda10443e4b55cc57db2e9573d
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07897595B2

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