Acetone → HCID 66558597, compound

HRID 1530611Notes

Reaction equation

HRID 1530611 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([O:7][C:8]2[CH:27]=[CH:26][C:11]3[C:12]4[N:16]([CH2:17][CH2:18][O:19][C:10]=3[CH:9]=2)[CH:15]=[C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[N:13]=4)[CH2:2]1.[CH3:28][C:29]([CH3:31])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOC(C)=O.O.CC(O)=O>[CH:29]([N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([O:7][C:8]2[CH:27]=[CH:26][C:11]3[C:12]4[N:16]([CH:15]=[C:14]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=5)[N:13]=4)[CH2:17][CH2:18][O:19][C:10]=3[CH:9]=2)[CH2:2]1)([CH3:31])[CH3:28]

Participants

9

Reactant 4

HCID 180AcetoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 68312735HCID 68312735, compound

Product 1

HCID 66558597HCID 66558597, compoundYield 76%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 8-(piperidin-3-yloxy)-2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene from Example 9 (13 mg, 0.036 mmol) in DCM (1 mL) were added acetone (100 uL), AcOH (50 uL) and sodium triacetoxyborohydride (15 mg, 0.072 mmol). The resulting mixture was stirred at RT for 18 h and then diluted with EtOAc. The organic layer was poured into water and the aqueous layer basified with a saturated solution of NaHCO3. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers were washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% 2M NH3/MeOH in DCM) affording 218 as a white solid (11 mg, 76%). LCMS: RT 2.05 min [M+H]+ 405.1. 1H NMR (CDCl3, 400 MHz): δ 8.57-8.51 (2H, m), 8.09 (1H, dt, J=7.95, 1.07 Hz), 7.72 (1H, td, J=7.72, 1.83 Hz), 7.61 (1H, s), 7.16-7.10 (1H, m), 6.75 (1H, dd, J=8.99, 2.58 Hz), 6.57 (1H, d, J=2.55 Hz), 4.50-4.45 (2H, m), 4.43-4.32 (3H, m), 3.13-3.07 (1H, m), 2.85-2.70 (2H, m), 2.26-2.10 (3H, m), 1.86-1.78 (1H, m), 1.48-1.36 (1H, m), 1.26 (1H, s), 1.04 (6H, d, J=6.57 Hz)

Workup

  1. extractionThe aqueous phase was extracted with EtOAc (×3)
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-a3a177a9b70c4a1f829eadaaf72433c6
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

Loading…