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Diisopropylethylamine → 5-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-N-(1-methyl-4-piperidyl)benzamide

HRID 2234310
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2234310
[Cl:1][C:2]1[C:3]([NH:12][C:13]2[N:23]=[C:22]3[C:16]([N:17]([CH3:30])[C:18](=[O:29])[CH2:19][CH2:20][N:21]3[CH:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)=[CH:15][N:14]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].[NH2:31][CH:32]1[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:1][C:2]1[C:3]([NH:12][C:13]2[N:23]=[C:22]3[C:16]([N:17]([CH3:30])[C:18](=[O:29])[CH2:19][CH2:20][N:21]3[CH:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)=[CH:15][N:14]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:31][CH:32]1[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]1)=[O:8]
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Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 686827155-Chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-benzoic acid2×

Produkt 1

HCID 68684906
5-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-N-(1-methyl-4-piperidyl)benzamide
Ausbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

5-chloro-4-[(2-cyclopentyl-6-methyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-2-fluoro-benzoic acid (Intermediate 219; 100 mg, 0.23 mmol), 4-amino-1-methylpiperidine (Fluorochem; 40 mg, 0.35 mmol) and HATU (132 mg, 0.35 mmol) were stirred in DMF (3 mL). N,N-diisopropylethylamine (121 μl, 0.69 mmol) was added and the mixture heated at 50° C. for 2 hours. The mixture was cooled and absorbed on to an SCX column, which was subsequently washed with methanol and eluted with ammonia in methanol. Product containing fractions were concentrated and the residue purified by base modified reverse phase preparative chromatography to yield the title compound as a white solid (58 mg, 48%)

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. customabsorbed on to an SCX column, which
  3. washwas subsequently washed with methanol
  4. washeluted with ammonia in methanol
  5. additionProduct containing fractions
  6. concentrationwere concentrated
  7. customthe residue purified by base modified reverse phase preparative chromatography

Quellen und Nachweise

ORD-Eintrag
ord-93f2d3aa61fc497a8870a121a0d1c2e2
Quelldatensatz
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07709471B2

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