Water → 2-(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)-4-chloropyrimidine

HRID 1796110Notes

Reaction equation

HRID 1796110 reaction equation
[CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[N:11]=1.[BH4-].[Na+].O>CC#N.CCOC(C)=O>[CH2:1]([N:19]1[CH2:18][CH:17]=[C:16]([C:12]2[N:11]=[C:10]([Cl:9])[CH:15]=[CH:14][N:13]=2)[CH2:21][CH2:20]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7503Benzyl ChlorideHCID 4311764Sodium borohydrideHCID 127647084-Chloro-2-(pyridin-4-yl)pyrimidine

Product 1

HCID 221807832-(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)-4-chloropyrimidineYield 57%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Benzyl chloride (460 μl, 4.0 mmol) was added to a stirred suspension of 4-chloro-2-(pyridin-4-yl)pyrimidine (prepared according to J. Med. Chem., 1982, 25(7), 837-842) (383 mg, 2.00 mmol) in MeCN (10 ml) and the mixture was heated at reflux for 30 h and then concentrated under reduced pressure. EtOH (5 ml) was then added, followed by NaBH4 (151 mg, 4.0 mmol), and the mixture stirred at room temperature for 30 min. Water (10 ml) and EtOAc (70 ml) were added, separated and the organics washed with H2O (20 ml), brine (20 ml) and concentrated under reduced pressure. The residue was purified by column chromatography on silica using 3% MeOH/CH2Cl2 as eluent to yield 2-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-4-chloropyrimidine (325 mg, 57%): 1H NMR (360 MHz, CDCl3) δ 8.52 (1H, d, J 5.3), 7.40-7.23 (6H, m), 7.11 (1H, d, J 5.3), 3.66 (2H, s), 3.30-3.20 (2H, m), 2.80-2.63 (4H, m); m/z (ES+) 286, 288 (1:1, M+H+).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 30 h
  3. concentrationconcentrated under reduced pressure
  4. additionEtOH (5 ml) was then added
  5. customseparated
  6. washthe organics washed with H2O (20 ml), brine (20 ml)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography on silica using 3% MeOH/CH2Cl2 as eluent

Sources & evidence

ORD record
ord-e3438f63608f41a7b4dba85addacdf3d
Source dataset
uspto-grants-2006_04
Patent number
US07030128B2

Reaction notes

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