Acetone → HCID 68312787, compound

HRID 1530721Notes

Reaction equation

HRID 1530721 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([N:23]5[CH2:26][CH2:25][C@@H:24]5[CH:27]5[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]5)[CH:20]=[CH:19][C:16]=43)[CH:10]=2)=[N:7][C:6]([CH3:33])=[N:5]1)([CH3:3])[CH3:2].[H][H].[CH3:36][C:37]([CH3:39])=O>[Pd]>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[C:16]4[CH:19]=[CH:20][C:21]([N:23]5[CH2:26][CH2:25][CH:24]5[C@@H:27]5[CH2:32][CH2:31][CH2:30][N:29]([CH:37]([CH3:39])[CH3:36])[CH2:28]5)=[CH:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][C:6]([CH3:33])=[N:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 180AcetoneHCID 68313119HCID 68313119, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 68312787HCID 68312787, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

To a solution of 2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-8-((R)-2-piperidin-3-ylazetidin-1-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (64.3 mg, 0.1436 mmol) in a mixture of IMS (5 mL) and acetone (1 mL) was added Pd/C (10%, 15 mg). The mixture was stirred at RT under a balloon of hydrogen for 16 h, then filtered through a celite pad. The filtrate was concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-15% 2M NH3/MeOH in DCM), then C18, gradient 20-60% MeOH in 0.5% TFA/H2O) and then loaded in MeOH onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH, affording 342 as a colourless foam (28 mg, 40%). LCMS (method K): RT 2.97 min [M+H]+ 490.2. 1H NMR (CD3OD, 400 MHz): δ 8.21 (1H, dd, J=8.7, 2.0 Hz), 7.61 (1H, s), 6.36-6.32 (1H, m), 6.13 (1H, dd, J=5.5, 2.3 Hz), 5.85 (1H, septet, J=6.6 Hz), 4.43 (4H, s), 4.10-3.91 (2H, m), 3.64 (1H, quintet, J=7.9 Hz), 3.06-2.87 (2H, m), 2.75 (1H, septet, J=6.4 Hz), 2.35 (3H, s), 2.33-2.08 (5H, m), 1.85-1.56 (3H, m), 1.51 (6H, d, J=6.6 Hz), 1.98 (0.5H, d, J=10.8 Hz), 1.25-1.11 (1H, m), 1.09 & 1.07 (6H, 2d, J=6.6 Hz)

Workup

  1. filtrationfiltered through a celite pad
  2. concentrationThe filtrate was concentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-15% 2M NH3/MeOH in DCM)
  4. washThe cartridge was washed with MeOH
  5. washthe product eluted with 0.5M NH3/MeOH

Sources & evidence

ORD record
ord-6bea674efb0a416b9a0a1c071274f4be
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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