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 2385935Notes

Reaction equation

HRID 2385935 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. 1 H NMR δ (ppm) (CDCl3): 8.30 (1H, d, J=8.17 Hz), 7.89 (1 H, s), 7.07 (1 H, dd, J=8.20, 1.83 Hz), 6.96 (1 H, d, J=1.81 Hz), 5.93-5.84 (1 H, m), 4.38 (2 H, t, J=5.05 Hz), 3.79 (2 H, t, J=7.00 Hz), 3.74-3.63 (1 H, m), 3.39 (2 H, t, J=5.06 Hz), 3.12 (2 H, m), 2.38 (1 H, m), 1.60 (6 H, d, J=6.63 Hz), 0.97 (6 H, 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-bfecb983234e496c8ca818e3a2709036
Source dataset
uspto-grants-2012_09
Patent number
US08263633B2

Reaction notes

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