Sulfuric Acid → HCID 58204967, compound

HRID 1498346Notes

Reaction equation

HRID 1498346 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([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]=43)[CH:10]=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[N:18]=[C:17]3[C:16]4[CH:19]=[CH:20][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:22][C:15]=4[O:14][CH2:13][CH2:12][N:11]3[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 67050666HCID 67050666, compound

Product 1

HCID 58204967HCID 58204967, compoundYield 60%

Procedure

To 2-{4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidin-1-yl}-2-methyl-propionitrile (312 mg, 0.70 mmol) was added concentrated sulfuric acid (3.5 mL). The resultant mixture was stirred for 3.5 hours at RT before being poured onto ice and basified with sodium carbonate. The aqueous mixture was extracted with 10% MeOH in DCM (×5). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash column chromatography (SiO2, gradient 0-10% MeOH in DCM), then triturated with diethyl ether (×3), to afford 287 (196 mg, 0.42 mmol, 60%). LCMS: RT=2.67 min, [M+H]+=464. 1H NMR δ (ppm) (DMSO-d): 8.27 (1 H, d, J=8.27 Hz), 7.86 (1 H, d, J=0.63 Hz), 7.85 (1 H, s), 7.17 (1 H, d, J=3.55 Hz), 7.03 (1 H, dd, J=8.34, 1.74 Hz), 6.91-6.89 (2 H, m), 5.89-5.79 (1 H, m), 4.48-4.41 (4 H, m), 2.80 (2 H, d, J=10.82 Hz), 2.17-2.09 (2 H, m), 1.77-1.60 (4 H, m), 1.44 (6 H, d, J=6.60 Hz), 1.05 (6 H, s). 1H obscured by solvent.

Workup

  1. extractionThe aqueous mixture was extracted with 10% MeOH in DCM (×5)
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resultant residue was purified by flash column chromatography (SiO2, gradient 0-10% MeOH in DCM)
  5. customtriturated with diethyl ether (×3)

Sources & evidence

ORD record
ord-38134974cfd749a9af84bd8ea896e8ff
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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