9-(piperidin-4-yl)-2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine → 2-[2-(2-Chloro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-piperidin-4-yl-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulene

HRID 1629181Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1629181
N1CCC(C2C=CC3OCCC4N(N=C(C5N(CC(F)(F)F)N=CN=5)C=4)C=3C=2)CC1.C(OC([N:38]1[CH2:43][CH:42]=[C:41]([C:44]2[CH:45]=[CH:46][C:47]3[O:56][CH2:55][CH2:54][C:53]4[C:49](=[N:50][N:51]([C:57]5[N:58]([C:62]6[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=6[Cl:68])[N:59]=[CH:60][N:61]=5)[CH:52]=4)[C:48]=3[CH:69]=2)[CH2:40][CH2:39]1)=O)(C)(C)C>>[Cl:68][C:63]1[CH:64]=[CH:65][CH:66]=[CH:67][C:62]=1[N:58]1[C:57]([N:51]2[N:50]=[C:49]3[C:53]([CH2:54][CH2:55][O:56][C:47]4[CH:46]=[CH:45][C:44]([CH:41]5[CH2:42][CH2:43][NH:38][CH2:39][CH2:40]5)=[CH:69][C:48]=43)=[CH:52]2)=[N:61][CH:60]=[N:59]1

Komponenten

3

Edukt 2

HCID 582048839-(piperidin-4-yl)-2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepineHCID 582048924-{2-[2-(2-Chloro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulen-9-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 513479062-[2-(2-Chloro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-piperidin-4-yl-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulene

Versuchsvorschrift

2-[2-(2-Chloro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-piperidin-4-yl-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulene was prepared similarly to 9-piperidin-4-yl-2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene from 4-{2-[2-(2-chloro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulen-9-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (490 mg, 0.9 mmol). The crude salt was partitioned between DCM and saturated aqueous sodium hydrogen carbonate, then the aqueous layer was extracted with DCM. The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to reverse phase HPLC (Gemini C18 column, gradient MeOH in H2O+0.1% HCO2H) to give 154 (80 mg, 18%) as the mono formate salt. 1H NMR (400 MHz, DMSO-d6): δ 8.44 (s, 1 H); 8.39 (s, 1 H); 8.27 (s, 1 H); 7.81-7.68 (m, 3 H); 7.64 (td, J=7.60, 1.51 Hz, 1 H); 7.09-7.03 (m, 2 H); 6.90 (d, J=8.28 Hz, 1 H); 4.19 (t, J=5.06 Hz, 2 H); 3.32 (d, J=12.42 Hz, 2 H); 3.04 (t, J=5.01 Hz, 2 H); 2.89 (dd, J=13.45, 11.09 Hz, 2 H); 2.54-2.56 (m, 1 H); 1.69 (d, J=13.20 Hz, 2 H); 1.58-1.45 (m, 2 H). LCMS: RT=7.99 min, M+H+=447

Aufarbeitung

  1. customThe crude salt was partitioned between DCM and saturated aqueous sodium hydrogen carbonate
  2. extractionthe aqueous layer was extracted with DCM
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-4d4f291053a84e99939fb7661b75406f
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785626B2

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