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 708198Notes

Reaction equation

HRID 708198 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-90f4cb53dbdb40ed8e6078b5082af539
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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