p-Toluenesulfonic acid → HCID 46223724, compound

HRID 2361548Notes

Reaction equation

HRID 2361548 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=3)[CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([NH:29][CH2:30][CH:31]2[CH2:33][CH2:32]2)(=[O:28])=[O:27])=[CH:22][CH:21]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C=O)C>[CH:31]1([CH2:30][NH:29][S:26]([C:23]2[CH:22]=[CH:21][C:20]([NH:19][C:2]3[N:7]=[C:6]([N:8]4[C:17]5[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=5)[CH2:11][CH2:10][CH2:9]4)[CH:5]=[CH:4][N:3]=3)=[CH:25][CH:24]=2)(=[O:28])=[O:27])[CH2:32][CH2:33]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 16788379Benzenesulfonamide, 4-amino-N-(cyclopropylmethyl)-HCID 86657556HCID 86657556, compound

Product 1

HCID 46223724HCID 46223724, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

The reaction flask containing 2,4-dichloropyrimidine (372 mg, 2.5 mmol), 6-methoxy-1,2,3,4-tetrahydroquinoline (489 mg, 3 mmol) and diisopropylethylamine (0.52 mL, 3 mmol) in n-butanol (10 mL) was heated at 40° C. overnight. The solvent was evaporated, and the residue was purified by flash column chromatography to give 2-Chloro-4-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)pyrimidine (551 mg, 80%). This intermediate (250 mg, 0.91 mmol) was then dissolved in dichloromethane and treated with BBr3 (1 M in dichloromethane) (1 mL, 1 mmol) at −78° C. The reaction mixture was slowly warmed up to room temperature and stirred for 1 hr, poured into water, extracted with dichloromethane. The combined organics were dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash column chromatography to give 2-Chloro-4-(6-hydroxy-3,4-dihydroquinolin-1(2H)-yl)pyrimidine (154 mg, 65%). To a stirred solution of 2-chloro-4-(6-hydroxy-3,4-dihydroquinolin-1(2H)-yl)pyrimidine (29 mg, 0.11 mmol) and 4-amino-N-(cyclopropylmethyl)benzenesulfonamide (27 mg, 0.12 mmol) in DMF (0.5 mL) was added p-toluenesulfonic acid (2 M in dioxane) (55 μL, 0.11 mmol). The reaction mixture was stirred at 90° C. overnight, then purified by HPLC to give the title compound (27 mg, 56%).

Workup

  1. custompurified by HPLC

Sources & evidence

ORD record
ord-c28ac70987704ba791da121f7d9fb1a3
Source dataset
uspto-grants-2014_04
Patent number
US08691573B2

Reaction notes

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