Acetone → HCID 58204621, compound

HRID 1498432Notes

Reaction equation

HRID 1498432 reaction equation
FC(F)(F)C(O)=O.[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[N:18]([CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=43)[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].[CH3:36][C:37]([CH3:39])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl.C(=O)([O-])O.[Na+]>[CH:8]([N:11]1[C:15]([C:16]2[N:25]=[C:24]3[C:23]4[CH:26]=[CH:27][C:28]([CH:30]5[CH2:35][CH2:34][N:33]([CH:37]([CH3:39])[CH3:36])[CH2:32][CH2:31]5)=[CH:29][C:22]=4[O:21][CH2:20][CH2:19][N:18]3[CH:17]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9]

Participants

7

Reactant 3

HCID 180Acetone2×HCID 5049666Sodium triacetoxyborohydride2×HCID 670507222-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt

Product 1

HCID 58204621HCID 58204621, compoundYield 8%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A suspension of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoro acetate (250 mg, 0.51 mmol) in DCE (5 mL) was added acetone (0.06 mL, 0.77 mmol) and 4 Å molecular sieves was stirred under an atmosphere of argon for 10 min before adding sodium triacetoxy borohydride (216 mg, 1.02 mmol) and stirring for 18 h at RT. Further acetone (0.06 mL) and sodium triacetoxyborohydride (216 mg) were added and stirring continued for a further 24 h. The reaction mixture was diluted with DCM and saturated aqueous sodium hydrogen carbonate and the organic layer washed with water followed by brine and then dried (MgSO4), filtered and concentrated in vacuo. The resultant solid was subjected to RPHPLC (gradient 20 to 70% methanol in water+0.1% HCO2H) to give 357 as a yellow solid (17 mg, 8%). LCMS: RT=2.81 min, [M+H]+=421. 1H NMR 400 MHz (DMSO-d) δ: 8.37-8.26 (1 H, m), 7.90-7.89 (2 H, m), 7.05 (1 H, dd, J=8.33, 1.81 Hz), 6.89 (1 H, d, J=1.73 Hz), 5.89-5.88 (1 H, m), 4.49-4.48 (4 H, m), 2.91 (2 H, d, J=10.95 Hz), 2.76-2.75 (1 H, m), 2.46 (1 H, s), 2.26 (2 H, t, J=11.38 Hz), 1.78 (2 H, d, J=12.43 Hz), 1.64 (2 H, td, J=12.20, 3.68 Hz), 1.48 (6H, d, J=6.60 Hz), 1.01 (6 H, d, J=6.57 Hz)

Workup

  1. stirringstirring for 18 h at RT
  2. stirringstirring
  3. waitcontinued for a further 24 h
  4. washthe organic layer washed with water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4400d23ad086414f8e03cc7d5a9913f7
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

Loading…