8-(3,6-Dihydro-2H-pyran-4-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene → 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-9-(tetrahydro-2H-pyran-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1629329Notes

Reaction equation

HRID 1629329 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:28]=[CH:27][C:10]3[C:11]4[N:15]([CH2:16][CH2:17][O:18][C:9]=3[CH:8]=2)[CH:14]=[C:13]([C:19]2[N:20]([CH:24]([CH3:26])[CH3:25])[N:21]=[CH:22][N:23]=2)[N:12]=4)[CH2:3][CH2:2]1>[OH-].[OH-].[Pd+2].C(OCC)(=O)C>[CH:24]([N:20]1[C:19]([C:13]2[N:12]=[C:11]3[C:10]4[CH:27]=[CH:28][C:7]([CH:4]5[CH2:5][CH2:6][O:1][CH2:2][CH2:3]5)=[CH:8][C:9]=4[O:18][CH2:17][CH2:16][N:15]3[CH:14]=2)=[N:23][CH:22]=[N:21]1)([CH3:26])[CH3:25]

Participants

4

Reactant 1

HCID 582046128-(3,6-Dihydro-2H-pyran-4-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

Product 1

HCID 582044972-(1-isopropyl-1H-1,2,4-triazol-5-yl)-9-(tetrahydro-2H-pyran-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 71%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 8-(3,6-dihydro-2H-pyran-4-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene (73 mg, 0.19 mmol), 20% palladium hydroxide on carbon (50 mg) and ethyl acetate (10 mL) was degassed then stirred at RT for 72 h under an atmosphere of hydrogen. The reaction mixture was filtered, the filtrate concentrated in vacuo and the residue triturated in cyclohexane to give 294 as a white solid (51 mg, 71%). LCMS: RT=4.30 min, [M+H]+=380 1H NMR 400 MHz (DMSO-d) δ: 8.34 (1 H, d, J=8.29 Hz), 7.91 (2 H, d, J=1.36 Hz), 7.08 (1 H, dd, J=8.34, 1.79 Hz), 6.92 (1 H, d, J=1.73 Hz), 5.90-5.89 (1 H, m), 4.50 (4 H, q, J=5.58 Hz), 3.96-3.95 (2 H, m), 3.44 (2 H, td, J=11.21, 3.01 Hz), 2.77-2.76 (1 H, m), 1.73-1.66 (4 H, m), 1.49 (6 H, d, J=6.60 Hz)

Workup

  1. customwas degassed
  2. filtrationThe reaction mixture was filtered
  3. concentrationthe filtrate concentrated in vacuo
  4. customthe residue triturated in cyclohexane

Sources & evidence

ORD record
ord-be2d145bee274df4801aa7c5b2c4c9dd
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

Loading…