Diisopropylethylamine → [3-Fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-carbamic Acid Tert-butyl Ester

HRID 220942Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 220942
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[C:12]([F:19])[CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][N:21]1[C:30]2[NH:29][C:28]3[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=3[NH:26][CH2:25][C:24]=2[CH:23]=[N:22]1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([N:26]2[CH2:25][C:24]3[CH:23]=[N:22][N:21]([CH3:20])[C:30]=3[NH:29][C:28]3[CH:31]=[CH:32][CH:33]=[CH:34][C:27]2=3)=[O:16])=[C:12]([F:19])[CH:11]=1)([CH3:2])([CH3:3])[CH3:4]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 187598234-(Boc-amino)methyl-2-fluoro-benzoic acidHCID 1357419771-Methyl-1,4,5,10-tetrahydrobenzo[b]pyrazolo[3,4-e][1,4]diazepine

Produkt 1

HCID 136128389[3-Fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzyl]-carbamic Acid Tert-butyl EsterAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 4-(tert-butoxycarbonylamino-methyl)-2-fluoro-benzoic acid from Example E2 (1.35 g, 5.0 mmol), 3-methyl-3,4,9,10-tetrahydro-2,3,4,9-tetraaza-benzo[f]azulene from Example E11 (11.0 g, 5.0 mmol) and PyBroP (3.03 g, 6.5 mmol) in dichloromethane (25 ml) and DIEA (1.31 ml, 7.5 mmol) was heated at reflux for 18 h. After cooling to room temperature, the mixture was washed with 5% KHCO3, 1M HCl then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; EtOAc) to yield the title compound (1.25 g, 56%).

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 18 h
  3. washthe mixture was washed with 5% KHCO3, 1M HCl
  4. dry with materialbrine, dried
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel (eluant; EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-a13ea8dec5184175b9022552736cf146
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202858B2

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