Diisopropylethylamine → HCID 46221496, Verbindung

HRID 1094781

Reaktionsgleichung

Reaktionsgleichung von HRID 1094781
[CH3:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[C:5]([N:11]2[N:15]=[CH:14][CH:13]=[N:12]2)=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[C@H:47]12[CH2:53][C@H:52]1[CH2:51][C@@H:50]([CH2:54][NH:55][C:56]1[CH:61]=[N:60][C:59]([C:62]([F:65])([F:64])[F:63])=[CH:58][N:57]=1)[NH:49][CH2:48]2.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][C:2]1[N:7]=[C:6]([C:8]([N:49]2[C@H:50]([CH2:54][NH:55][C:56]3[CH:61]=[N:60][C:59]([C:62]([F:65])([F:63])[F:64])=[CH:58][N:57]=3)[CH2:51][C@H:52]3[C@H:47]([CH2:53]3)[CH2:48]2)=[O:10])[C:5]([N:11]2[N:15]=[CH:14][CH:13]=[N:12]2)=[CH:4][CH:3]=1

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 593637336-methyl-3-(2H-1,2,3-triazol-2-yl)picolinic acidHCID 59396007N-[(1S,4S,6S)-3-azabicyclo[4.1.0]hept-4-ylmethyl]-5-(trifluoromethyl)-2-pyrazinamine

Produkt 1

HCID 46221496HCID 46221496, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

6-methyl-3-(2H-1,2,3-triazol-2-yl)-2-pyridinecarboxylic acid D40 (33.0 mg) was dissolved in 1 ml of DCM, then TBTU (61.3 mg, 0.191 mmol) and DIPEA (0.033 ml, 0.191 mmol) were added. The suspension was stirred for 30 minutes at room temperature. N-[(1S,4S,6S)-3-azabicyclo[4.1.0]hept-4-ylmethyl]-5-(trifluoromethyl)-2-pyrazinamine D31 (40 mg) dissolved in 1 ml of DCM was added and the reaction was stirred overnight at room temperature. 3 ml of NaHCO3 saturated solution were added, and the aqueous layer was extracted with DCM. The organic layers were collected together, dried through a phase separator and concentrated under vacuum to give a crude which was purified by SCX chromatography (column size 5 g). A second purification was performed by Silica —NH chromatography (Biotage SP—column size 25 g, using Cy:EtOAc=5:5 to EtOAc). It was recovered the title compound E6 (30 mg). UPLC: (Acid Final_QC): rt=0.76 and 0.80 minutes (rotamers present), peaks observed: 459 (M+1). C21H21F3N8O requires 458. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.38 (s, 1 H) 8.28-8.22 (m, 1 H) 8.08-8.06 (s, 2 H), 7.90-7.78 (m, 2 H), 7.57-7.51 (m, 1 H) 4.20-4.08 (m, 1 H) 3.76-3.40 (m, 3 H), 2.68-2.61 (m, 1 H), 2.56 (s, 3 H), 2.44-2.35 (m, 1 H), 1.28-0.95 (m, 2 H), 0.92-0.83 (m, 1 H), 0.68-0.60 (m, 1 H), 0.24-0.18 (m, 1 H).

Aufarbeitung

  1. additionwas added
  2. stirringthe reaction was stirred overnight at room temperature
  3. extractionthe aqueous layer was extracted with DCM
  4. customThe organic layers were collected together
  5. customdried through a phase separator
  6. concentrationconcentrated under vacuum
  7. customto give a crude which
  8. customwas purified by SCX chromatography (column size 5 g)
  9. customA second purification
  10. customIt was recovered the title compound E6 (30 mg)
  11. customrt=0.76 and 0.80 minutes (rotamers present)

Quellen und Nachweise

ORD-Eintrag
ord-a945bddd27e84642a23adfeb52a2abab
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08133908B2

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