Diisopropylethylamine → HCID 178520726, Verbindung

HRID 2378989Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2378989
[Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][C:22]([F:25])([F:24])[F:23])[C:13](=[O:20])[C@H:14]([CH2:16][C:17]([OH:19])=O)[CH2:15][C:8]=3[CH:7]=[C:6]([Cl:26])[C:5]=2[NH:4][N:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH:49]1[CH2:54][CH2:53][CH:52]([N:55]2[CH2:61][CH2:60][C:59]3[CH:62]=[CH:63][CH:64]=[CH:65][C:58]=3[NH:57][C:56]2=[O:66])[CH2:51][CH2:50]1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][C:22]([F:25])([F:24])[F:23])[C:13](=[O:20])[C@H:14]([CH2:16][C:17](=[O:19])[N:49]4[CH2:50][CH2:51][CH:52]([N:55]5[CH2:61][CH2:60][C:59]6[CH:62]=[CH:63][CH:64]=[CH:65][C:58]=6[NH:57][C:56]5=[O:66])[CH2:53][CH2:54]4)[CH2:15][C:8]=3[CH:7]=[C:6]([Cl:26])[C:5]=2[NH:4][N:3]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 178525538HCID 178525538, Verbindung

Produkt 1

HCID 178520726HCID 178520726, VerbindungAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(S)-2-(1,4-Dichloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino [3,4-e]indazol-7-yl)acetic acid(95 mg, 0.232 mmol) was dissolved in N,N-dimethylformamide (2.0 ml). TBTU (79 mg, 0.246 mmol) was added to the mixture followed by 3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one (72 mg, 0.293 mmol) and then N,N-diisopropylethylamine (150 μl, 0.861 mmol). Reaction stirred at room temperature for 4 hours. Reaction was quenched with 50% acetonitrile-water. Material was purified by reverse phase prep HPLC (water-acetonitrile-trifluoroacetic acid). Acetonitrile was removed from the fractions by roto-vap. Remaining aqueous was made basic with aqueous sodium bicarbonate. Material was extracted twice with ethyl acetate and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Title compound was obtained as white solid in 59% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.88 (s, 1H) 8.49 (s, 1 H) 7.35 (s, 1H) 7.00-7.09 (m, 3H) 6.70-6.87 (m, 1H) 5.42 (s, 2H) 4.49 (d, J=12.51 Hz, 1H) 4.36-4.45 (m, 1H) 4.25-4.36 (m, 1H) 4.11-4.24 (m, 1H) 3.91-4.10 (m, 2H) 3.34-3.41 (m, 2H) 3.19 (d, J=18.01 Hz, 1H) 3.05-3.15 (m, 1H) 2.93-3.03 (m, 1H) 2.83-2.93 (m, 3H) 2.53-2.65 (m, 1H) 2.32-2.47 (m, 1H) 1.57-1.87 (m, 3H) 1.44-1.57 (m, 1H). High resolution MS m/e (M+H)−=637.1735.

Aufarbeitung

  1. customReaction
  2. customReaction
  3. customwas quenched with 50% acetonitrile-water
  4. customMaterial was purified by reverse phase prep HPLC (water-acetonitrile-trifluoroacetic acid)
  5. customAcetonitrile was removed from the fractions by roto-vap
  6. extractionMaterial was extracted twice with ethyl acetate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-1aec1cea0dca4e54aeb8a93bc30dda79
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07470680B2

Notizen zur Reaktion

Wird geladen…