Sulfuric Acid → 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}-isobutyramide

HRID 708230Notes

Reaction equation

HRID 708230 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]=[C:21]([CH:23]5[CH2:28][CH2:27][N:26]([C:29]([CH3:33])([CH3:32])[C:30]#[N:31])[CH2:25][CH2:24]5)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].S(=O)(=O)(O)[OH:35].C(=O)([O-])[O-].[Na+].[Na+]>>[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]=[C:21]([CH:23]5[CH2:28][CH2:27][N:26]([C:29]([CH3:33])([CH3:32])[C:30]([NH2:31])=[O:35])[CH2:25][CH2:24]5)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 582040722-{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}-2-methyl-propionitrile

Product 1

HCID 582041362-{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}-isobutyramideYield 19%

Procedure

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}-2-methyl-propionitrile (346 mg, ˜50% pure, ˜0.40 mmol) was treated with concentrated sulphuric acid (5 mL) and the mixture was stirred for 5.5 hours then diluted with ice chips (˜50 mL) and made basic with solid sodium carbonate. The mixture was extracted with 10% MeOH in DCM (×4) and the combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 0-5% MeOH in DCM first time then 0-100% EtOAc in DCM) to give 483 as a white solid (36 mg, 19%). LCMS: RT=3.28 min, [M+H]+=481. 1H NMR δ (ppm) (DMSO-d6): 9.54 (1H, s), 8.27 (1H, d, J=8.13 Hz), 8.05 (1H, s), 7.98 (1H, s), 7.86 (1H, s), 7.05 (1H, d, J=8.29 Hz), 6.90 (1H, s), 5.81-5.73 (1H, m), 4.32 (2H, s), 3.41-3.30 (4H, m), 3.12 (1H, m), 2.83 (1H, m), 2.13 (2H, d, J=13.80 Hz), 1.99 (1H, d, J=13.56 Hz), 1.72 (1H, s), 1.50 (12H, d, J=6.50 Hz). 1 Proton obscured by water peak

Workup

  1. additionthen diluted with ice chips (˜50 mL)
  2. extractionThe mixture was extracted with 10% MeOH in DCM (×4)
  3. dry with materialthe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography (SiO2, 0-5% MeOH in DCM first time

Sources & evidence

ORD record
ord-2061173fe87b47e9863cd8054d62b2d5
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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