N-(tert-butoxycarbonyl)glycine → {[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylcarbamoyl]-methyl}-carbamic Acid Tert-butyl Ester

HRID 220972

Reaktionsgleichung

Reaktionsgleichung von HRID 220972
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([O:29][C:30]([NH:32][CH2:33][C:34]([OH:36])=O)=[O:31])([CH3:28])([CH3:27])[CH3:26].Cl.[NH2:38][CH2:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]([N:48]2[CH2:57][C:56]3[CH:55]=[N:54][N:53]([CH3:58])[C:52]=3[NH:51][C:50]3[CH:59]=[C:60]([Cl:63])[CH:61]=[CH:62][C:49]2=3)=[O:47])=[CH:42][C:41]=1[F:64].C1C(N=NC2C(=O)N(C3C=CC(S([O-])(=O)=O)=CC=3)N=C2C([O-])=O)=CC=C(S([O-])(=O)=O)C=1.[Na+].[Na+].[Na+].CC1C=C2N=C3C(=NC(NC3=O)=O)N(C[C@H](O)[C@H](O)[C@H](O)COP([O-])(O)=O)C2=CC=1C.[Na+].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:25]([O:29][C:30](=[O:31])[NH:32][CH2:33][C:34](=[O:36])[NH:38][CH2:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]([N:48]2[CH2:57][C:56]3[CH:55]=[N:54][N:53]([CH3:58])[C:52]=3[NH:51][C:50]3[CH:59]=[C:60]([Cl:63])[CH:61]=[CH:62][C:49]2=3)=[O:47])=[CH:42][C:41]=1[F:64])([CH3:26])([CH3:27])[CH3:28]

Komponenten

9

Edukt 6

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 164825TartrazineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 23666409Riboflavin sodium phosphateHCID 136346648(4-Aminomethyl-3-fluoro-phenyl)-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone Hydrochloride

Produkt 1

HCID 136128360{[4-(6-Chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-2-fluoro-benzylcarbamoyl]-methyl}-carbamic Acid Tert-butyl EsterAusbeute 100 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

HBTU (165 mg, 0.44 mmol) was added to a solution of N-(tert-butoxycarbonyl)glycine (65 mg, 0.37 mmol) in DMF (10 ml) and the mixture was stirred for 30 min at room temperature. (4-Aminomethyl-3-fluoro-phenyl)-(6-chloro-3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulen-9-yl)-methanone hydrochloride from Example E102.2 (100 mg, 0.22 mmol) and DIEA (0.228 ml, 1.31 mmol) were added and the mixture was stirred for 24 h at room temperature. The solution was diluted with EtOAc, washed with water then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 5% methanol:95% dichloromethane then 10% methanol:90% dichloromethane) to give a white solid identified as the title compound (123 mg, 100%).

Aufarbeitung

  1. stirringthe mixture was stirred for 24 h at room temperature
  2. washwashed with water
  3. dry with materialbrine, dried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel (eluant
  6. custom5% methanol:95% dichloromethane then 10% methanol:90% dichloromethane) to give a white solid

Quellen und Nachweise

ORD-Eintrag
ord-a89dc96d42fa4bc8abfc1921e26ea43e
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202858B2

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