HCID 68313039, compound → HCID 68312701, compound

HRID 1530699Notes

Reaction equation

HRID 1530699 reaction equation
C([N:8]1[CH2:11][C:10]([CH2:36][CH:37]2[CH2:39][CH2:38]2)([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:37]1([CH2:36][C:10]2([O:12][C:13]3[CH:35]=[CH:34][C:16]4[C:17]5[N:21]([CH:20]=[C:19]([C:25]6[N:26]([CH:31]([CH3:32])[CH3:33])[N:27]=[C:28]([CH3:30])[N:29]=6)[N:18]=5)[CH2:22][CH2:23][O:24][C:15]=4[CH:14]=3)[CH2:11][NH:8][CH2:9]2)[CH2:38][CH2:39]1

Participants

4

Reactant 1

HCID 68313039HCID 68313039, compound

Product 2

HCID 21705897Ammonia methanolYield 10%HCID 68312701HCID 68312701, compoundYield 38.6%

Reagents, catalysts & solvents 1

HCID 9942167Palladium hydroxideCatalyst

Procedure

To a solution of 8-(1-benzyl-3-cyclopropylmethylazetidin-3-yloxy)-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (65 mg, 0.124 mmol) in IMS (8 mL) was added Pd(OH)2/C (20 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 Pd(OH)2/C (30 mg) was added to the filtrate which was stirred at RT under a hydrogen atmosphere for a further 10 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 20-55% 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 purification by column chromatography (Si-PCC, gradient 3-12% MeOH in DCM then 10-15% 2M NH3/MeOH in DCM) afforded 284 as a colourless foam (10.4 mg, 19%). LCMS (Method K): RT 2.96 min [M+H]+ 435.1. 1H NMR (CD3OD, 400 MHz): δ 8.33 (1H, d, J=9.0 Hz), 7.67 (1H, s), 6.55 (1H, dd, J=8.9, 2.5 Hz), 6.34 (1H, d, J=2.5 Hz), 5.87 (1H, septet, J=6.6 Hz), 4.48 (4H, s), 3.94 (2H, d, J=10.0 Hz), 3.80 (2H, d, J=10.0 Hz), 2.36 (3H, s), 2.06 (2H, d, J=6.6 Hz), 1.52 (6H, d, J=6.6 Hz), 0.83-0.73 (1H, m), 0.48-0.43 (2H, m), 0.06-0.02 (2H, m)

Workup

  1. filtrationThe suspension was then filtered through a pad of Celite® and Pd(OH)2/C (30 mg)
  2. additionwas added to the filtrate which
  3. stirringwas stirred at RT under a hydrogen atmosphere for a further 10 h
  4. filtrationThe suspension was then filtered through a pad of Celite®
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (C18, gradient 20-55% MeOH in 0.5% TFA/H2O)
  7. washThe cartridge was washed with MeOH
  8. washthe product eluted with 0.5M NH3/MeOH
  9. customFurther purification by column chromatography (Si-PCC, gradient 3-12% MeOH in DCM

Sources & evidence

ORD record
ord-622a9d1f21f0411dac861f6203a4299b
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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