Triethylamine → 8-(1-Ethenesulfonyl-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 707831Notes

Reaction equation

HRID 707831 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.C(N(CC)CC)C.Cl[CH2:42][CH2:43][S:44](Cl)(=[O:46])=[O:45]>C(Cl)Cl>[CH:43]([S:44]([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)(=[O:46])=[O:45])=[CH2:42]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 15385Ethanesulfonylchloride, 2-chloro-HCID 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 670505818-(1-Ethenesulfonyl-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 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a mixture 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 (100 mg, 0.2 mmol) in dry DCM (2 mL) was added triethylamine (60 μL, 0.4 mmol) and the reaction mixture was stirred for 1 hour. The mixture was washed with water followed by brine, dried (Na2SO4) and then treated with triethylamine (30 μL, 0.2 mmol) followed by 2-chloroethane-sulfonyl chloride (42 μL, 0.4 mmol) in dry DCM (1 mL). The reaction mixture was stirred at RT for 18 hours then diluted with DCM and washed with water followed by brine, dried (Na2SO4) and concentrated in vacuo to give 8-(1-Ethenesulfonyl-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 as a light brown oil (75 mg, 82%). 1H NMR δ (ppm) (CDCl3): 8.39 (1H, d, J=8.22 Hz), 7.93 (1H, s), 7.16 (1H, dd, J=8.22, 1.98 Hz), 7.02 (1H, d, J=1.91 Hz), 6.61 (1H, dd, J=16.50, 9.95 Hz), 6.39 (1H, d, J=16.66 Hz), 6.18 (1H, d, J=9.95 Hz), 5.93-5.87 (1H, m), 4.45-4.39 (2H, m), 4.28-4.22 (2H, m), 4.07-3.97 (2H, m), 3.81 (1H, t, J=7.81 Hz), 3.46-3.40 (2H, m), 1.64 (6H, d, J=6.65 Hz)

Workup

  1. washThe mixture was washed with water
  2. dry with materialdried (Na2SO4)
  3. stirringThe reaction mixture was stirred at RT for 18 hours
  4. washwashed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ce299d8223674ee3b3dd2f3cd5c7fa0b
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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