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 1799980Notes

Reaction equation

HRID 1799980 reaction equation
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

Participants

3

Reactant 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

Product 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

Procedure

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, 1H); 8.39 (s, 1H); 8.27 (s, 1H); 7.81-7.68 (m, 3H); 7.64 (td, J=7.60, 1.51 Hz, 1H); 7.09-7.03 (m, 2H); 6.90 (d, J=8.28 Hz, 1H); 4.19 (t, J=5.06 Hz, 2H); 3.32 (d, J=12.42 Hz, 2H); 3.04 (t, J=5.01 Hz, 2H); 2.89 (dd, J=13.45, 11.09 Hz, 2H); 2.54-2.56 (m, 1H); 1.69 (d, J=13.20 Hz, 2H); 1.58-1.45 (m, 2H). LCMS: RT=7.99 min, M+H+=447

Workup

  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

Sources & evidence

ORD record
ord-51b8bcf292124e7a9f296f6c1e46c87a
Source dataset
uspto-grants-2013_01
Patent number
US08343955B2

Reaction notes

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