Dimethylamine → (2-{3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidine-1-sulfonyl}-ethyl)-dimethyl-amine

HRID 1190656Notes

Reaction equation

HRID 1190656 reaction equation
[CH:1]([S:3]([N:6]1[CH2:9][CH:8]([C:10]2[CH:31]=[CH:30][C:13]3[C:14]4[N:15]=[C:16]([C:22]5[N:23]([CH:27]([CH3:29])[CH3:28])[N:24]=[CH:25][N:26]=5)[S:17][C:18]=4[CH2:19][CH2:20][O:21][C:12]=3[CH:11]=2)[CH2:7]1)(=[O:5])=[O:4])=[CH2:2].[CH3:32][NH:33][CH3:34]>>[CH:27]([N:23]1[C:22]([C:16]2[S:17][C:18]3[CH2:19][CH2:20][O:21][C:12]4[CH:11]=[C:10]([CH:8]5[CH2:7][N:6]([S:3]([CH2:1][CH2:2][N:33]([CH3:34])[CH3:32])(=[O:5])=[O:4])[CH2:9]5)[CH:31]=[CH:30][C:13]=4[C:14]=3[N:15]=2)=[N:26][CH:25]=[N:24]1)([CH3:28])[CH3:29]

Participants

3

Reactant 2

HCID 674DimethylamineHCID 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]azulene

Product 1

HCID 58204046(2-{3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidine-1-sulfonyl}-ethyl)-dimethyl-amineYield 50.3%

Procedure

To a suspension of 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 (75 mg, 0.17 mmol) in IMS (2 mL) was added dimethylamine (2M in MeOH, 158 μL, 0.32 mmol) and the reaction mixture was stirred for 72 hours. The mixture was concentrated in vacuo to low volume and partitioned between DCM and water. The layers were separated and the organic layer was washed with water followed by brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was combined with a previous batch of the desired compound and purified by flash chromatography (SiO2, 0-2% MeOH in DCM) to give 455 as a white solid (43 mg, 34%). LCMS: RT=8.51 min, [M+H]+=503. 1H NMR δ (ppm) (CDCl3): 8.36 (1H, d, J=8.20 Hz), 7.90 (1H, s), 7.16 (1H, dd, J=8.24, 1.92 Hz), 7.03 (1H, d, J=1.88 Hz), 5.93-5.83 (1H, m), 4.39 (2H, t, J=5.04 Hz), 4.26 (2H, t, J=8.23 Hz), 4.10 (2H, t, J=7.33 Hz), 3.81-3.74 (1H, m), 3.40 (2H, t, J=5.05 Hz), 3.22-3.14 (2H, m), 2.81 (2H, t, J=7.47 Hz), 2.29 (6H, s), 1.61 (6H, d, J=6.63 Hz)

Workup

  1. concentrationThe mixture was concentrated in vacuo to low volume
  2. custompartitioned between DCM and water
  3. customThe layers were separated
  4. washthe organic layer was washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography (SiO2, 0-2% MeOH in DCM)

Sources & evidence

ORD record
ord-34d98c1fb4284a938de94c44eb8ee4ee
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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