1,4-Dioxane hydrochloride → 2-{3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-9-yl]-azetidin-1-yl}-ethanol

HRID 708126Notes

Reaction equation

HRID 708126 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[CH:21][C:20]([CH:23]5[CH2:26][N:25]([CH2:27][CH2:28][O:29]C6CCCCO6)[CH2:24]5)=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].Cl.O1CCOCC1>CO.C(Cl)Cl>[CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[CH:21][C:20]([CH:23]5[CH2:24][N:25]([CH2:27][CH2:28][OH:29])[CH2:26]5)=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 582039862-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-9-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-azetidin-3-yl}-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

Product 1

HCID 582041282-{3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-9-yl]-azetidin-1-yl}-ethanolYield 32%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-9-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-azetidin-3-yl}-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene (110 mg, 0.22 mmol) in MeOH (3 mL) and DCM (3 mL) was treated with 4N HCl/dioxan (2 mL, 8 mmol) and the mixture left to stand for 3 hours then concentrated in vacuo. The resultant residue was triturated with diethyl ether and dried under vacuum. Further purification by flash chromatography (SiO2, 0-10% 2N NH3/MeOH in DCM) gave 376 (29 mg, 32%). LCMS: RT=6.96 min, [M+H]+=412. 1H NMR δ (ppm) (CDCl3): 8.31 (1H, d, J=2.34 Hz), 7.90 (1H, s), 7.15 (1H, dd, J=8.27, 2.35 Hz), 7.01 (1H, d, J=8.26 Hz), 5.94-5.84 (1H, m), 4.40-4.34 (2H, m), 3.89-3.83 (2H, m), 3.84-3.72 (1H, m), 3.59-3.54 (2H, m), 3.41-3.36 (2H, m), 3.28-3.21 (2H, m), 2.71-2.66 (2H, m), 1.62 (6H, d, J=6.65 Hz). 1 Exchangeable proton not seen

Workup

  1. waitthe mixture left
  2. concentrationthen concentrated in vacuo
  3. customThe resultant residue was triturated with diethyl ether
  4. customdried under vacuum
  5. customFurther purification by flash chromatography (SiO2, 0-10% 2N NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-aa448556011b45a48cf09d2714780a8c
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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