Aluminum(III) Chloride → Cavosonstat

HRID 55786Notes

Reaction equation

HRID 55786 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:21]C)[CH:17]=2)[N:12]=1)[C:5]([OH:7])=[O:6].[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([OH:21])[CH:17]=2)[N:12]=1)[C:5]([OH:7])=[O:6]

Participants

4

Reactant 2

HCID 6451240Aluminum(III) ChlorideHCID 669800633-Chloro-4-(6-methoxyquinolin-2-yl)benzoic acid

Product 1

HCID 56960912CavosonstatYield 18%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-chloro-4-(6-methoxyquinolin-2-yl)benzoic acid (150 mg, 0.479 mmol) in anhydrous CH2Cl2 (5 mL) was added AlCl3 (320 mg, 2.40 mmol). The reaction mixture was refluxed overnight. The mixture was quenched with saturated NH4Cl (10 mL) and the aqueous layer was extracted with CH2Cl2/MeOH (v/v=10:1, 30 mL×3). The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated to give the crude product, which was purified by prep-HPLC (0.1% TFA as additive) to give 3-chloro-4-(6-hydroxyquinolin-2-yl)benzoic acid (25 mg, yield 18%). 1H NMR (DMSO, 400 MHz): δ 10.20 (brs, 1H), 8.30 (d, J=8.4 Hz, 1H), 8.10-8.00 (m, 2H), 7.95 (d, J=9.2 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.72 (d, J=8.8 Hz, 1H), 7.38 (dd, J=6.4, 2.8 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), MS (ESI): m/z 299.9 [M+H]+.

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. customThe mixture was quenched with saturated NH4Cl (10 mL)
  3. extractionthe aqueous layer was extracted with CH2Cl2/MeOH (v/v=10:1, 30 mL×3)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record
ord-5a3ee1ae877f442580d3e9b003e5e95e
Source dataset
uspto-grants-2016_09
Patent number
US09433618B2

Reaction notes

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