Triethylamine → 2-{-4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidin-1-yl}-ethanesulfonic acid dimethylamide

HRID 1849424Notes

Reaction equation

HRID 1849424 reaction equation
OC(C(F)(F)F)=O.[CH:8]([N:11]1[C:15]([C:16]2[S:17][C:18]3[CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=4[C:24]=3[N:25]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].C(N(CC)CC)C.[CH3:43][N:44]([CH3:50])[S:45]([CH:48]=[CH2:49])(=[O:47])=[O:46]>>[CH3:43][N:44]([CH3:50])[S:45]([CH2:48][CH2:49][N:33]1[CH2:34][CH2:35][CH:30]([C:28]2[CH:27]=[CH:26][C:23]3[C:24]4[N:25]=[C:16]([C:15]5[N:11]([CH:8]([CH3:10])[CH3:9])[N:12]=[CH:13][N:14]=5)[S:17][C:18]=4[CH2:19][CH2:20][O:21][C:22]=3[CH:29]=2)[CH2:31][CH2:32]1)(=[O:47])=[O:46]

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 19037148N,N-dimethylethene-1-sulfonamideHCID 866523172-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt

Product 1

HCID 582039912-{-4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidin-1-yl}-ethanesulfonic acid dimethylamideYield 74%

Procedure

To a solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt 375 (188 mg, 0.37 mmol) and triethylamine (0.18 mL, 1.3 mmol) in IMS (3 mL) was added ethenesulfonic acid dimethylamide and the reaction mixture stirred at RT for 18 h before being concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 5% MeOH in DCM) to give 499 as a beige solid (145 mg, 74%). LCMS: RT=3.47 min, [M+H]+=531. 1H NMR δ (ppm) (DMSO-d6): 8.23 (1 H, d, J=8.19 Hz), 8.05 (1 H, s), 7.04 (1 H, dd, J=8.26, 1.80 Hz), 6.88 (1 H, d, J=1.76 Hz), 5.82-5.72 (1 H, m), 4.30 (2 H, t, J=5.02 Hz), 3.37 (2 H, t, J=5.04 Hz), 3.19 (2 H, t, J=7.23 Hz), 2.95 (2 H, d, J=10.97 Hz), 2.75 (6 H, s), 2.65 (2 H, t, J=7.25 Hz), 2.04 (2 H, t, J=11.43 Hz), 1.75 (2 H, d, J=12.62 Hz), 1.67-1.53 (2 H, m), 1.50 (6 H, d, J=6.58 Hz). 1 H obscured by solvent

Workup

  1. concentrationbefore being concentrated in vacuo

Sources & evidence

ORD record
ord-51fe4bf061694cf6874f3d6ac4cebcf8
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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