HCID 68312636, compound → HCID 68312824, compound

HRID 1530686Notes

Reaction equation

HRID 1530686 reaction equation
C([N:8]1[CH2:11][C:10]([CH3:36])([O:12][C:13]2[CH:35]=[CH:34][C:16]3[C:17]4[N:21]([CH2:22][CH2:23][O:24][C:15]=3[CH:14]=2)[CH:20]=[C:19]([C:25]2[N:26]([CH:31]([CH3:33])[CH3:32])[N:27]=[C:28]([CH3:30])[N:29]=2)[N:18]=4)[CH2:9]1)C1C=CC=CC=1>[OH-].[OH-].[Pd+2]>[NH3:8].[CH3:10][OH:12].[CH:31]([N:26]1[C:25]([C:19]2[N:18]=[C:17]3[C:16]4[CH:34]=[CH:35][C:13]([O:12][C:10]5([CH3:36])[CH2:11][NH:8][CH2:9]5)=[CH:14][C:15]=4[O:24][CH2:23][CH2:22][N:21]3[CH:20]=2)=[N:29][C:28]([CH3:30])=[N:27]1)([CH3:33])[CH3:32]

Participants

4

Reactant 1

HCID 68312636HCID 68312636, compound

Product 2

HCID 21705897Ammonia methanolYield 2%HCID 68312824HCID 68312824, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 9942167Palladium hydroxideCatalyst

Procedure

To a solution of 8-(1-benzyl-3-methylazetidin-3-yloxy)-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (31 mg, 0.064 mmol) in IMS (5 mL) was added Pd(OH)2/C (11 mg) and the reaction mixture was stirred at RT under a hydrogen atmosphere for 16 h. The suspension was then filtered through a pad of Celite® and the filtrate was concentrated in vacuo. The resulting residue was purified by column chromatography (C18, gradient 15-50% MeOH in 0.5% TFA/H2O) and then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH. Further purifications by column chromatography (Si-PCC, gradient 2-12% 2M NH3/MeOH in DCM) and then (Si-PCC, gradient 3-33% MeOH in DCM) afforded 271 as a colourless gum (5.3 mg, 21%). LCMS (Method K): RT 2.57 min [M+H]+ 395.1. 1H NMR (CD3OD, 400 MHz): δ 8.33 (1H, d, J=9.0 Hz), 7.67 (1H, s), 6.55 (1H, dd, J=9.0, 2.6 Hz), 6.35 (1H, d, J=2.5 Hz), 5.87 (1H, septet, J=6.7 Hz), 4.48 (4H, s), 3.95 (2H, d, J=9.4 Hz), 3.60 (2H, d, J=9.4 Hz), 2.35 (3H, s), 1.70 (3H, s), 1.52 (6H, d, J=6.6 Hz)

Workup

  1. filtrationThe suspension was then filtered through a pad of Celite®
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (C18, gradient 15-50% MeOH in 0.5% TFA/H2O)
  4. washThe cartridge was washed with MeOH
  5. washthe product eluted with 0.5M NH3/MeOH

Sources & evidence

ORD record
ord-05e0f682e3904b83a3e3bd25ecd294f4
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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