Hydrochloric Acid → HCID 67252242, compound

HRID 1798274Notes

Reaction equation

HRID 1798274 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([OH:17])[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2].Cl[C:20]1[N:25]=[N:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=1.[H-].[Na+].[NH4+].[Cl-].Cl>C1COCC1>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:20]3[N:25]=[N:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 133828716-Chloropyridazine-3-carbonitrileHCID 58292549Ethyl 2-(1,6-dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

Product 1

HCID 67252242HCID 67252242, compoundYield 54.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (1,6-dihydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (1.0 g, 3.9 mmol) and 6-chloro-pyridazine-3-carbonitrile (1.12 g, 7.9 mmol) in THF (50 mL) at 0° C. was added NaH (0.38 g) in portions. The reaction mixture was allowed to warm to room temperature and stirred for 12 hours. Saturated NH4Cl (10 mL) was added at 0° C. and the solution acidified to pH˜4 with 1N HCl. The mixture was extracted with EtOAc (2×15 mL) and the organic extracts washed with water (10 mL), dried and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (DCM:MeOH 95:5) to give [6-(6-cyano-pyridazin-3-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (0.75 g, 53%). 1H NMR (400 MHz, CDCl3): δ 9.27 (s, 1H), 8.36 (d, J=9.2 Hz, 1H), 7.71 (d, J=9.2 Hz, 1H), 7.33 (d, J=2.0 Hz, 1H), 7.18 (d, J=1.6 Hz, 1H), 5.55 (dd, J=2.4, 9.2 Hz, 1H), 4.04 (q, J=6.8 Hz, 2H), 3.14 (dd, J=2.4, 15.6 Hz, 1H), 2.36-2.32 (m, 1H), 2.31 (s, 3H), 1.13 (t, J=6.8 Hz, 3H). MS (ESI) m/z=354 [M+H]+.

Workup

  1. extractionThe mixture was extracted with EtOAc (2×15 mL)
  2. washthe organic extracts washed with water (10 mL)
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel flash column chromatography (DCM:MeOH 95:5)

Sources & evidence

ORD record
ord-be89ae0518524eea87d51ba97aee5766
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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