Triethylamine → HCID 69421266, compound

HRID 1178874Notes

Reaction equation

HRID 1178874 reaction equation
Cl.Cl.[CH2:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][N:4]1[CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.[CH2:18]([N:20](CC)CC)C.[C:25]1([CH3:35])[CH:30]=[CH:29][CH:28]=[C:27]([S:31](Cl)(=[O:33])=[O:32])[CH:26]=1.[OH-].[Na+]>CN(C)C1C=CN=CC=1.ClCCl>[CH3:35][C:25]1[CH:26]=[C:27]([S:31]([N:20]([CH3:18])[C@H:15]2[CH2:16][CH2:17][C@H:13]([N:4]3[CH2:5][CH2:6][C:7]4[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=4)[CH2:3]3)[CH2:14]2)(=[O:33])=[O:32])[CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 27345953-Methylbenzenesulphonyl chlorideHCID 86597524HCID 86597524, compound

Product 1

HCID 69421266HCID 69421266, compoundYield 31.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of cis/trans-1-methylamino-3-(3-(1,2,3,4-tetrahydroisoquinolin-2-yl)cyclopentane dihydrochloride (139.6 mg, 0.46 mmol), triethylamine (250 μl, 1.8 mmol), 4-dimethylaminopyridine (6.3 mg, 0.05 mmol) and 3-toluenesulfonyl chloride (91.8 mg, 0.48 mmol) in dichloromethane (10 ml) was stirred at room temperature overnight (18 h). The reaction mixture was poured into 1M aqueous sodium hydroxide (20 ml), the phases separated and the aqueous extracted with more dichloromethane (10 ml). The combined organics were dried (MgSO4) and evaporated. The residue was purified by medium pressure silica chromatography, eluting with 5% methanol in dichloromethane, to afford trans-3,N-dimethyl-N-(3-(1,2,3,4-tetrahydroisoquinolin-2-yl)cyclopentyl)benzenesulfonamide (55.6 mg, 31%) as the first eluted isomer followed by cis-3,N-dimethyl-N-(3-(1,2,3,4-tetrahydroisoquinolin-2-yl)cyclopentyl)benzenesulfonamide (41.2 mg, 23%). The hydrochloride salts were prepared by treating ethyl acetate solutions with hydrogen chloride in diethyl ether. trans-3,N-Dimethyl-N-(3-(1,2,3,4-tetrahydroisoquinolin-2-yl)cyclopentyl) -benzenesulfonamide hydrochloride; δH (400 MHz, CD3OD) 1.60-1.86 (3H, m), 2.02-2.16 (2H, m), 2.30 (1H, m), 2.44 (3H, s), 2.77 (3H, s), 3.18 (2H, br s), 3.55 (2H, v br s), 3.77 (1H, m), 4.42 (2H, br s), 4.60 (1H, m), 7.21 (1H, m), 7.25-7.33 (3H, m), 7.48 (2H, m), 7.65 (2H, m); m/z (ES+) 385 ([M+H]+, 100%). cis-3,N-Dimethyl-N-(3-(1,2,3,4-tetrahydroisoquinolin-2-yl)cyclopentyl) -benzenesulfonamide hydrochloride; δH (400 MHz, CD3OD) 1.72 (2H, m), 1.89 (2H, m), 2.17-2.31 (2H, m), 2.44 (3H, s), 2.81 (3H, s), 3.19 (2H, br s), 3.5 (2H, v br s), 3.71 (1H, m), 4.4 (2H, v br s), 4.47 (1H, m), 7.20 (1H, m), 7.28 (3H, m), 7.47 (2H, m), 7.65 (2H, m); m/z (ES+) 385 ([M+H]+, 100%).

Workup

  1. customthe phases separated
  2. extractionthe aqueous extracted with more dichloromethane (10 ml)
  3. dry with materialThe combined organics were dried (MgSO4)
  4. customevaporated
  5. customThe residue was purified by medium pressure silica chromatography
  6. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-1725599488534763a5b4026795f0c804
Source dataset
uspto-grants-2007_10
Patent number
US07276607B2

Reaction notes

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