Diisopropylethylamine → HCID 178512335, Verbindung

HRID 132502

Reaktionsgleichung

Reaktionsgleichung von HRID 132502
[NH2:1][C@H:2]1[C:16](=[O:17])[N:15]([CH2:18][C:19]([F:22])([F:21])[F:20])[CH2:14][C:5]2[C:6]3[CH:7]=[N:8][NH:9][C:10]=3[C:11]([Cl:13])=[CH:12][C:4]=2[CH2:3]1.C(N(CC)C(C)C)(C)C.C1C=CC(O[C:39](OC2C=CC=CC=2)=[N:40][C:41]#[N:42])=CC=1.Cl.[NH:51]1[CH2:56][CH2:55][CH:54]([C:57]2[C:58](=[O:67])[NH:59][C:60]3[C:65]([CH:66]=2)=[CH:64][CH:63]=[CH:62][CH:61]=3)[CH2:53][CH2:52]1>CN(C)C=O.CO>[Cl:13][C:11]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:14][N:15]([CH2:18][C:19]([F:21])([F:20])[F:22])[C:16](=[O:17])[C@H:2]([NH:1][C:39]([N:51]3[CH2:52][CH2:53][CH:54]([C:57]4[C:58](=[O:67])[NH:59][C:60]5[C:65]([CH:66]=4)=[CH:64][CH:63]=[CH:62][CH:61]=5)[CH2:55][CH2:56]3)=[N:40][C:41]#[N:42])[CH2:3][C:4]=2[CH:12]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 688090Diphenyl N-CyanocarbonimidateHCID 59732089(7R)-7-amino-4-chloro-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-oneHCID 673176623-piperidin-4-yl-1H-quinolin-2-one;hydrochloride

Produkt 1

HCID 178512335HCID 178512335, VerbindungAusbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(R)-7-Amino-4-chloro-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one (130 mg, 390.7 μmol) was dissolved in N,N-dimethylformamide (5.0 mL). N,N-Diisopropylethylamine (200 μL, 1.1 mmol) was added to the mixture followed by diphenyl N-cyanocarbonimidate (100 mg, 407.1 μmol). Mixture stirred at room temperature for 40 minutes. 3-(Piperidin-4-yl)quinolin-2(1H)-one hydrochloride (125 mg; 472.1 μmol) was added to the vessel with stirring. The mixture was heated to 100° C. and held for 54 hr with stirring. Mixture was cooled to room temperature and then diluted with methanol. Mixture was filtered. Filtrate was purified by reverse phase prep HPLC (acetonitrile-water-ammonium acetate). Acetonitrile was removed from the fractions by roto-vap. Remaining aqueous was diluted with water. Solids were filtered off and washed with water. Air was pulled through the filter cake for 2 hours. Solids were collected and then dried in vacuo. Title compound was obtained as tan solid in 33% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.62 (s, 1 H) 11.79 (s, 1 H) 8.35 (s, 1H) 7.73 (s, 1 H) 7.66 (d, J=7.94 Hz, 1H) 7.53 (d, J=7.93 Hz, 1H) 7.44 (t, J=7.63 Hz, 1 H) 7.25-7.33 (m, 2 H) 7.16 (t, J=7.48 Hz, 1 H) 5.59-5.71 (m, 1 H) 5.40 (d, J=17.40 Hz, 1 H) 4.90 (d, J=17.70 Hz, 1 H) 4.59-4.77 (m, 1 H) 4.27 (d, J=13.12 Hz, 2H) 4.00-4.15 (m, 1 H) 3.33-3.42 (m, 1 H) 3.03-3.26 (m, 4 H) 1.86-1.98 (m, 2) 1.54-1.71 (m, 2 H). High resolution MS m/e (M+H)+=611.1890.

Aufarbeitung

  1. stirringwith stirring
  2. temperatureThe mixture was heated to 100° C.
  3. waitheld for 54 hr
  4. stirringwith stirring
  5. temperatureMixture was cooled to room temperature
  6. filtrationMixture was filtered
  7. customFiltrate was purified by reverse phase prep HPLC (acetonitrile-water-ammonium acetate)
  8. customAcetonitrile was removed from the fractions by roto-vap
  9. additionRemaining aqueous was diluted with water
  10. filtrationSolids were filtered off
  11. washwashed with water
  12. waitAir was pulled through the filter cake for 2 hours
  13. customSolids were collected
  14. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-823b3163e19c48559f0ad4f254d067ed
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07384931B2

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