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 1190704Notes

Reaction equation

HRID 1190704 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 (1H, d, J=8.19 Hz), 8.05 (1H, s), 7.04 (1H, dd, J=8.26, 1.80 Hz), 6.88 (1H, d, J=1.76 Hz), 5.82-5.72 (1H, m), 4.30 (2H, t, J=5.02 Hz), 3.37 (2H, t, J=5.04 Hz), 3.19 (2H, t, J=7.23 Hz), 2.95 (2H, d, J=10.97 Hz), 2.75 (6H, s), 2.65 (2H, t, J=7.25 Hz), 2.04 (2H, t, J=11.43 Hz), 1.75 (2H, d, J=12.62 Hz), 1.67-1.53 (2H, m), 1.50 (6H, d, J=6.58 Hz). 1H obscured by solvent

Workup

  1. concentrationbefore being concentrated in vacuo

Sources & evidence

ORD record
ord-bb435f090a64400eacdda735e31b27b1
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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