Triethylamine → 5,6-Dimethyl-2-(4-fluorophenylamino)-4-(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine hydrochloride

HRID 275947Notes

Reaction equation

HRID 275947 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:16][C:17]1[C:18]([N:25]2[CH2:34][CH2:33][C:32]3[C:27](=[CH:28][C:29]([OH:36])=[C:30]([OH:35])[CH:31]=3)[CH:26]2[CH3:37])=[N:19][C:20]([Cl:24])=[N:21][C:22]=1[CH3:23].[OH-].[Na+]>ClCCl>[ClH:24].[CH3:16][C:17]1[C:18]([N:25]2[CH2:34][CH2:33][C:32]3[C:27](=[CH:28][C:29]([OH:36])=[C:30]([OH:35])[CH:31]=3)[CH:26]2[CH3:37])=[N:19][C:20]([NH:6][C:5]2[CH:7]=[CH:8][C:2]([F:1])=[CH:3][CH:4]=2)=[N:21][C:22]=1[CH3:23]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 97314-FluoroanilineHCID 14798Sodium HydroxideHCID 183156425,6-Dimethyl-2-chloro-4-(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine

Product 1

HCID 183157675,6-Dimethyl-2-(4-fluorophenylamino)-4-(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine hydrochlorideYield 39.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

4-fluoroaniline(0.46 ml, 4.70 mmol) and triethylamine(0.66 ml, 4.70 mmol) were added to a solution of 5,6-dimethyl-2-chloro-4-(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine(1.0 g, 3.13 mmol) in dimethyifomiamide(5 ml) and then stirred for 3 hours at 120° C. The reaction mixture was cooled to a room temperature and diluted with dichloromethane. Aqueous sodium hydroxide solution was added to the reaction mixture, which was then stirred. The dichloromethane layer was dried over anhydrous magnesium sulfate, concentrated under a reduced pressure. The resulting residue was purified by a silica gel column chromatography and dissolved in ethanol. Ethyl ether saturated with hydrochloric acid was added to the solution. The resulting solid was filtered and dried to give 530 mg of the titled compound.

Workup

  1. temperatureThe reaction mixture was cooled to a room temperature
  2. stirringwas then stirred
  3. dry with materialThe dichloromethane layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under a reduced pressure
  5. customThe resulting residue was purified by a silica gel column chromatography
  6. dissolutiondissolved in ethanol
  7. additionEthyl ether saturated with hydrochloric acid was added to the solution
  8. filtrationThe resulting solid was filtered
  9. customdried

Sources & evidence

ORD record
ord-fc71dce9d64347e8946127750024bf2e
Source dataset
uspto-grants-2002_03
Patent number
US06352993B1

Reaction notes

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