Sulfuric Acid → 7-Benzyl-3-chloro-2-chloromethyl-4-(3,4,-dimethoxyphenyl)-5,6,7,8-tetrahydrothieno-[2,3-b:5,4-c']dipyridine

HRID 1003226Notes

Reaction equation

HRID 1003226 reaction equation
[NH2:1][C:2]1[S:17][C:5]2[CH2:6][N:7]([CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:8][CH2:9][C:4]=2[C:3]=1[C:18](=O)[C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=1.[Cl:30][CH2:31][C:32]([CH2:34][Cl:35])=O.S(=O)(=O)(O)O>C(O)(=O)C>[CH2:10]([N:7]1[CH2:8][CH2:9][C:4]2[C:3]3[C:2]([S:17][C:5]=2[CH2:6]1)=[N:1][C:32]([CH2:34][Cl:35])=[C:31]([Cl:30])[C:18]=3[C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 107931,3-DichloroacetoneHCID 10763972HCID 10763972, compound

Product 1

HCID 154626447-Benzyl-3-chloro-2-chloromethyl-4-(3,4,-dimethoxyphenyl)-5,6,7,8-tetrahydrothieno-[2,3-b:5,4-c']dipyridineYield 29%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-amino-6-benzyl-3-(3,4-dimethoxybenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine (10.0 g), 1,3-dichloroacetone (3.4 g), concentrated sulfuric acid (2.6 g) and acetic acid (200 ml) was stirred at 90° C. for 4 hours. After the reaction mixture was concentrated under reduced pressure, the residue was alkalinized with 2 N NaOH and then extracted with dichloromethane. The dichloromethane layer was washed with water and dried (MgSO4), after which the solvent was distilled off. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:1, v/v) to yield 7-benzyl-3-chloro-2-chloromethyl-4-(3,4,-dimethoxyphenyl)-5,6,7,8-tetrahydrothieno-[2,3-b:5,4-c']dipyridine (for structural formula, see below) (3.5 g, 29%), which was then recrystallized from ethyl acetate-hexane to yield colorless prismatic crystals having a melting point of 171 to 172° C. ##STR61##

Workup

  1. concentrationAfter the reaction mixture was concentrated under reduced pressure
  2. extractionextracted with dichloromethane
  3. washThe dichloromethane layer was washed with water
  4. dry with materialdried (MgSO4)
  5. distillationafter which the solvent was distilled off
  6. washeluted with ethyl acetate-hexane (1:1

Sources & evidence

ORD record
ord-989b6c7170b849eca031d4d6a89ffb06
Source dataset
uspto-grants-2000_04
Patent number
US06046189

Reaction notes

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