Acetone → 8-(1-isopropyl-azetidin-3-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

HRID 1190619Notes

Reaction equation

HRID 1190619 reaction equation
OC(C(F)(F)F)=O.[NH:8]1[CH2:11][CH:10]([C:12]2[CH:33]=[CH:32][C:15]3[C:16]4[N:17]=[C:18]([C:24]5[N:25]([CH:29]([CH3:31])[CH3:30])[N:26]=[CH:27][N:28]=5)[S:19][C:20]=4[CH2:21][CH2:22][O:23][C:14]=3[CH:13]=2)[CH2:9]1.[CH3:34][C:35]([CH3:37])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl.C(Cl)Cl>[CH:35]([N:8]1[CH2:11][CH:10]([C:12]2[CH:33]=[CH:32][C:15]3[C:16]4[N:17]=[C:18]([C:24]5[N:25]([CH:29]([CH3:31])[CH3:30])[N:26]=[CH:27][N:28]=5)[S:19][C:20]=4[CH2:21][CH2:22][O:23][C:14]=3[CH:13]=2)[CH2:9]1)([CH3:37])[CH3:34]

Participants

7

Reactant 4

HCID 180AcetoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 866523168-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt

Product 1

HCID 582042038-(1-isopropyl-azetidin-3-yl)-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azuleneYield 63%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 8-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt 235 (215 mg, 0.45 mmol) in dry DCE (4.5 mL) under argon was treated with acetone (49 μL, 0.67 mmol) followed by sodium triacetoxyborohydride (190 mg, 0.89 mmol). The reaction mixture was stirred at RT for 18 hours. Aqueous saturated sodium bicarbonate solution and DCM were added and the phases were separated. The aqueous phase was extracted with DCM (×2) and the combined organic phase was washed with water followed by brine, dried (Na2SO4) and concentrated in vacuo. The resultant solid was triturated with ether, to give 423 as an off-white solid (115 mg, 63%). LCMS: RT=7.44 min, [M+H]+=410. 1H NMR δ (ppm) (CDCl3): 8.30 (1H, d, J=8.17 Hz), 7.89 (1H, s), 7.07 (1H, dd, J=8.20, 1.83 Hz), 6.96 (1H, d, J=1.81 Hz), 5.93-5.84 (1H, m), 4.38 (2H, t, J=5.05 Hz), 3.79 (2H, t, J=7.00 Hz), 3.74-3.63 (1H, m), 3.39 (2H, t, J=5.06 Hz), 3.12 (2H, m), 2.38 (1H, m), 1.60 (6H, d, J=6.63 Hz), 0.97 (6H, d, J=6.21 Hz)

Workup

  1. customthe phases were separated
  2. extractionThe aqueous phase was extracted with DCM (×2)
  3. washthe combined organic phase was washed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant solid was triturated with ether

Sources & evidence

ORD record
ord-7a2d07d05c5e400384aa43297a60b984
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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