Acetic Acid → HCID 66558596, compound

HRID 1530610Notes

Reaction equation

HRID 1530610 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][CH:4]([CH:8]([O:10][C:11]2[CH:33]=[CH:32][C:14]3[C:15]4[N:19]([CH2:20][CH2:21][O:22][C:13]=3[CH:12]=2)[CH:18]=[C:17]([C:23]2[N:24]([CH:29]([CH3:31])[CH3:30])[N:25]=[C:26]([CH3:28])[N:27]=2)[N:16]=4)[CH3:9])[CH2:3][CH2:2]1.[CH3:34][C:35]([CH3:37])=O.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.O.CO>[CH:29]([N:24]1[C:23]([C:17]2[N:16]=[C:15]3[C:14]4[CH:32]=[CH:33][C:11]([O:10][CH:8]([CH:4]5[CH2:5][CH2:6][CH2:7][N:1]([CH:35]([CH3:37])[CH3:34])[CH2:2][CH2:3]5)[CH3:9])=[CH:12][C:13]=4[O:22][CH2:21][CH2:20][N:19]3[CH:18]=2)=[N:27][C:26]([CH3:28])=[N:25]1)([CH3:30])[CH3:31]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 68313155HCID 68313155, compound

Product 1

HCID 66558596HCID 66558596, compoundYield 88.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 8-(1-azepan-4-ylethoxy)-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene from Example 10 (50 mg, 0.11 mmol) in a 10:1 mixture of DCM:MeOH (2.2 mL) were added acetone (81 uL, 1.1 mmol), AcOH (0.011 mmol) and sodium triacetoxyborohydride (47 mg, 0.22 mmol). The reaction mixture was stirred for 24 h at RT, then diluted with DCM and poured into water. The aqueous layer was extracted with DCM (×3) and the combined organic phases 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 217 as a white solid (48 mg, 81%). LCMS: RT 3.16 min [M+H]+ 493.2. 1H NMR (CDCl3, 400 MHz): δ 8.40 (1H, d, J=8.95 Hz), 7.56 (1H, s), 6.71 (1H, d, J=9.07 Hz), 6.52 (1H, s), 5.98-5.86 (1H, m), 4.52-4.44 (2H, m), 4.43-4.36 (2H, m), 4.33-4.23 (1H, m), 2.92-2.80 (1H, m), 2.76-2.48 (5H, m), 2.41 (3H, s), 2.02-1.74 (5H, m), 1.63-1.40 (7H, m), 1.30-1.23 (3H, m), 1.03-0.95 (6H, m)

Workup

  1. extractionThe aqueous layer was extracted with DCM (×3)
  2. washthe combined organic phases 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-5dd3d7bd50c64fa9a6978ba90a7d6e9e
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

Loading…