Acetone → HCID 68312707, compound

HRID 1530609Notes

Reaction equation

HRID 1530609 reaction equation
C(OC([N:11]1[CH2:16][CH2:15][CH:14]([CH:17]([O:19][C:20]2[CH:42]=[CH:41][C:23]3[C:24]4[N:28]([CH2:29][CH2:30][O:31][C:22]=3[CH:21]=2)[CH:27]=[C:26]([C:32]2[N:33]([CH:38]([CH3:40])[CH3:39])[N:34]=[C:35]([CH3:37])[N:36]=2)[N:25]=4)[CH3:18])[CH2:13][CH2:12]1)=O)C1C=CC=CC=1.[CH3:43][C:44]([CH3:46])=O>CO.[Pd]>[CH:38]([N:33]1[C:32]([C:26]2[N:25]=[C:24]3[C:23]4[CH:41]=[CH:42][C:20]([O:19][CH:17]([CH:14]5[CH2:15][CH2:16][N:11]([CH:44]([CH3:46])[CH3:43])[CH2:12][CH2:13]5)[CH3:18])=[CH:21][C:22]=4[O:31][CH2:30][CH2:29][N:28]3[CH:27]=2)=[N:36][C:35]([CH3:37])=[N:34]1)([CH3:39])[CH3:40]

Participants

5

Reactant 2

HCID 180AcetoneHCID 68313033HCID 68313033, compound

Product 1

HCID 68312707HCID 68312707, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 4-{1-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy]ethyl}piperidine-1-carboxylic acid benzyl ester from Example 11 (60 mg, 0.10 mmol) in acetone (2 mL) and MeOH (0.5 mL) was added 10% Pd/C (50 mg). The reaction mixture was stirred at RT under a hydrogen atmosphere for 48 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 (Si-PCC, gradient 0-10% 2M NH3/MeOH in DCM) affording 216 (20 mg, 42%). LCMS: RT 3.03 min [M+H]+ 379.2. 1H NMR (CDCl3, 400 MHz): δ 8.39 (1H, d, J=8.96 Hz), 7.56 (1H, s), 6.70 (1H, dd, J=8.98, 2.55 Hz), 6.52 (1H, d, J=2.51 Hz), 5.99-5.84 (1H, m), 4.51-4.34 (4H, m), 4.19 (1H, m), 3.00-2.78 (2H, m), 2.77-2.63 (1H, m), 2.41 (3H, s), 2.18-2.05 (3H, m), 1.95-1.85 (1H, m), 1.77-1.67 (1H, m), 1.56 (6H, d, J=8.76 Hz), 1.52-1.32 (2H, m), 1.28 (3H, d, J=8.24 Hz), 1.05 (6H, d, J=6.54 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 (Si-PCC, gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-5d46ea3f8c714235b70f8b83721fd17d
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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