Hydrochloric Acid → 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

HRID 1629162Notes

Reaction equation

HRID 1629162 reaction equation
C(OC([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:15]=[CH:16][C:17]3[O:26][CH2:25][CH2:24][C:23]4[N:19]([N:20]=[C:21]([C:27]5[N:28]([CH2:32][C:33]([F:36])([F:35])[F:34])[N:29]=[CH:30][N:31]=5)[CH:22]=4)[C:18]=3[CH:37]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C(OCC)C>[Pd]>[NH:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[CH:16][C:17]3[O:26][CH2:25][CH2:24][C:23]4[N:19]([N:20]=[C:21]([C:27]5[N:28]([CH2:32][C:33]([F:35])([F:34])[F:36])[N:29]=[CH:30][N:31]=5)[CH:22]=4)[C:18]=3[CH:37]=2)[CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 582047464-{2-[2-(2,2,2-Trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulen-9-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert butyl ester

Product 1

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]oxazepineYield 74%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

A solution of 4-{2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulen-9-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert butyl ester (232 mg, 0.41 mmol) in IMS (10 mL) was treated with a slurry of Pd/C (170 mg, 10% wt Pd on carbon, 50% water) in IMS. The mixture was degassed then the atmosphere evacuated and back-filled with hydrogen and then stirred at RT for 18 h. The reaction mixture was filtered through Ceilte® with ethyl acetate washings and the filtrate concentrated in vacuo. The resultant residue was dissolved in methanol (5 mL), treated with 1M HCl in diethyl ether (2 mL, 2 mmol) and the mixture stirred at RT for 18 h. Solvent was removed in vacuo and residue triturated in diethyl ether to give 130 as a pale yellow solid (127 mg, 74%). 1H NMR (DMSO-d6, 400 MHz): δ 9.08-8.97 (br m, 1 H); 8.96-8.81 (br m, 1 H); 8.22 (s, 1 H); 7.69 (s, 1 H); 7.31-7.23 (m, 2 H); 6.99 (s, 1 H); 5.72 (q, J=8.8 Hz, 2 H); 4.51 (t, J=6.1 Hz, 2 H); 3.42-3.32 (m, 2 H); 3.22-3.15 (m, 2 H); 3.08-2.88 (m, 3 H); 2.04-1.95 (m, 2 H); 1.94-1.80 (m, 2 H). LCMS: RT=6.75 min, M+H+=419.2

Workup

  1. customThe mixture was degassed
  2. customthe atmosphere evacuated
  3. additionback-filled with hydrogen
  4. filtrationThe reaction mixture was filtered through Ceilte® with ethyl acetate washings
  5. concentrationthe filtrate concentrated in vacuo
  6. dissolutionThe resultant residue was dissolved in methanol (5 mL)
  7. stirringthe mixture stirred at RT for 18 h
  8. customSolvent was removed in vacuo and residue
  9. customtriturated in diethyl ether

Sources & evidence

ORD record
ord-bf7e28aef9e24195a33abe53680b58cd
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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