Sodium Bicarbonate → 3-(4-Fluorobenzoyl)-8-(3-methoxyphenyl)-1,2,3,6-tetrahydroazepino[4,5-B]indole-5-carboxylic acid ethyl ester

HRID 37949Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 37949
[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[C:16](Br)[CH:17]=[CH:18][C:19]=3[C:11]=2[CH2:10][CH2:9][N:8]([C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH:7]=1)=[O:5])[CH3:2].[CH3:30][O:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.CCO.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[C:16]([C:36]4[CH:35]=[CH:34][CH:33]=[C:32]([O:31][CH3:30])[CH:37]=4)[CH:17]=[CH:18][C:19]=3[C:11]=2[CH2:10][CH2:9][N:8]([C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH:7]=1)=[O:5])[CH3:2]

Komponenten

7

Edukt 3

HCID 516892Sodium BicarbonateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 575591468-Bromo-3-(4-fluorobenzoyl)-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester

Produkt 1

HCID 575591333-(4-Fluorobenzoyl)-8-(3-methoxyphenyl)-1,2,3,6-tetrahydroazepino[4,5-B]indole-5-carboxylic acid ethyl esterAusbeute 93,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 21863594Toluene ethanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred solution of 8-bromo-3-(4-fluorobenzoyl)-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester (compound in Example 37A, 70 mg, 0.15 mmol), 3-methoxyphenylboronic acid (58 mg, 0.38 mmol), and (o-tolyl)3P (24 mg, 0.077 mmol) in toluene/EtOH (2:1, 3 mL) was added 0.55 mL of 1M NaHCO3 solution and Pd(OAc)2 (7 mg) at ambient temperature. The reaction mixture was heated at 80° C. under N2 for 1.5 hours and samples monitored by LC-MS. The solution was diluted with DCM (10 mL) and washed with brine. The aqueous phase was extracted with DCM (10 mL) twice. The combined organic phase was dried over Na2SO4 and concentrated. The crude product was purified by flash chromatograph on silica gel, eluting with EtOAc-hexane (0-30%) to yield the title compound (68 mg) as a light yellow solid; 1H-NMR (CDCl3): δ 10.76 (1H, s), 8.20 (1H, s), 7.78 (4H, m), 7.52 (2H, m), 7.42 (1H, d), 7.36 (3H, m), 7.04 (1H, m), 4.43 (4H, m), 4.05 (3H, s), 3.45 (2H, m), 1.39 (3H, t). MS (ESI): 485 (MH+).

Aufarbeitung

  1. washwashed with brine
  2. extractionThe aqueous phase was extracted with DCM (10 mL) twice
  3. dry with materialThe combined organic phase was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatograph on silica gel
  6. washeluting with EtOAc-hexane (0-30%)

Quellen und Nachweise

ORD-Eintrag
ord-8dda85203ab345528a91eb0b26ef9e96
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524704B2

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