Triethylamine → PBT-1033

HRID 1754097Notes

Reaction equation

HRID 1754097 reaction equation
[CH2:1]([N:3](CC)[CH2:4]C)C.[Cl:8][C:9]1[CH:18]=[C:17]([Cl:19])[C:16]([OH:20])=[C:15]2[C:10]=1[CH:11]=[CH:12][C:13]([CH:21]=O)=[N:14]2.Cl.CNC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.ClCCl>[ClH:8].[Cl:8][C:9]1[CH:18]=[C:17]([Cl:19])[C:16]([OH:20])=[C:15]2[C:10]=1[CH:11]=[CH:12][C:13]([CH2:21][N:3]([CH3:4])[CH3:1])=[N:14]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 573761135,7-Dichloro-8-hydroxyquinoline-2-carbaldehyde

Product 1

HCID 46911781PBT-1033Yield 73%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

Triethylamine (0.55 mL) was added dropwise to a stirred solution of 5,7-dichloro-8-hydroxyquinoline-2-carboxaldehyde 17 (1.0 g, 4.13 mmol) and dimethylamine hydrochloride (365 mg, 4.48 mmol) in 1,2-dichloroethane (50 mL). After 5 minutes, sodium triacetoxyborohydride (1.2 g, 5.66 mmol) was added portionwise over 5 minutes. The mixture was then allowed to stir at RT overnight. Dichloromethane (100 mL) was added, the mixture washed with saturated sodium bicarbonate (50 mL×3), dried (Na2SO4), and concentrated. The resulting residue was extracted with diethyl ether (50 mL×4), the ethereal extracts combined and concentrated. Concentrated hydrochloric acid (5 mL) was then added and the mixture concentrated in vacuo. The process was repeated twice. The residue, after washing with dichloromethane, gave 5,7-dichloro-2-dimethylaminomethyl-quinolin-8-ol hydrochloride (PBT 1033) as a pale straw-coloured solid (0.96 g, 73%). 1H NMR (DMSO-d6, 400 MHz): δ 10.80 (s, 1 H), 10.40 (br, 1 H), 8.60 (d, J=8.6, 1 H), 7.92 (s, 1 H), 7.78 (d, J=8.6, 1 H), 4.83 (d, J=5.3, 2 H), 2.94 (s, 3 H), 2.92 (s, 3 H).

Workup

  1. washthe mixture washed with saturated sodium bicarbonate (50 mL×3)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. extractionThe resulting residue was extracted with diethyl ether (50 mL×4)
  5. concentrationconcentrated
  6. additionConcentrated hydrochloric acid (5 mL) was then added
  7. concentrationthe mixture concentrated in vacuo
  8. washThe residue, after washing with dichloromethane

Sources & evidence

ORD record
ord-9744b1adc5134d3e8733316495336a55
Source dataset
uspto-grants-2015_10
Patent number
US09169211B2

Reaction notes

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