Betahistine → 1-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-[N-{2-(2-pyridyl)ethyl}-N-methylaminomethyl]-4-pyridone

HRID 495527Notes

Reaction equation

HRID 495527 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=1.[F:11][C:12]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:13]=1[CH2:14][N:15]1[C:20]([CH3:21])=[C:19]([CH:22]=C=O)[C:18](=[O:25])[C:17]([Br:26])=[C:16]1[CH3:27].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.O>[F:11][C:12]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:13]=1[CH2:14][N:15]1[C:20]([CH3:21])=[C:19]([CH2:22][N:2]([CH2:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=2)[CH3:1])[C:18](=[O:25])[C:17]([Br:26])=[C:16]1[CH3:27]

Participants

6

Reactant 3

HCID 2366BetahistineHCID 5049666Sodium triacetoxyborohydrideHCID 223272351-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-(carbonylmethyl)4-pyridone

Product 1

HCID 223272811-(2,6-Difluorobenzyl)-2,6-dimethyl-3-bromo-5-[N-{2-(2-pyridyl)ethyl}-N-methylaminomethyl]-4-pyridone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

(2-Methylaminoethyl)pyridine (680 mg, 5.00 mmol) was added to a stirred solution of 1-(2,6-difluorobenzyl)-2,6-dimethyl-3-bromo-5-(carbonylmethyl)4-pyridone (430 mg, 1.16 mmol) in CH2Cl2 (15 mL). After 30 min., NaBH(OAc)3 (1.23 g, 5.80 mmol) was added in small portions, and the resulting mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with H2O (15 mL) and the organic layer was separated and washed with sat. NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated in vacuo. The crude was used in the next step without any further purification. Crude yield 426 mg (75%). LRMS m/z 490.0 (M+−1), 492.0 (M++1).

Workup

  1. customthe organic layer was separated
  2. washwashed with sat. NaHCO3 and brine
  3. dry with materialThe organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude was used in the next step without any further purification

Sources & evidence

ORD record
ord-bbe82732e8a74440ba67a863363dd5d3
Source dataset
uspto-grants-2005_09
Patent number
US06939883B2

Reaction notes

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