Triethylamine → benzyl (NE)-N-[[1-[1-(4-fluorophenyl)cyclobutyl]-7-[2-(propylsulfonylamino)ethoxy]-3,4-dihydro-1H-isoquinolin-2-yl]-(phenylmethoxycarbonylamino)methylidene]carbamate

HRID 242073Notes

Reaction equation

HRID 242073 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:12]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH2:23][CH2:24][NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:28])=[O:27])[CH:20]=4)[CH2:15][CH2:14][NH:13]3)[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CS[C:34]([NH:46][C:47](=[O:56])[O:48][CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[N:35][C:36](=[O:45])[O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C(N(CC)CC)C>CN(C)C=O.FC(F)(F)S([O-])(=O)=O.[Ag+]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:12]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH2:23][CH2:24][NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:27])=[O:28])[CH:20]=4)[CH2:15][CH2:14][N:13]3/[C:34](/[NH:46][C:47](=[O:56])[O:48][CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[N:35]/[C:36](=[O:45])[O:37][CH2:38][C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH2:9][CH2:10][CH2:11]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 46642131,3-Bis(benzyloxycarbonyl)-2-methylisothioureaHCID 66868509N-[2-({1-[1-(4-Fluorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}oxy)ethyl]propane-1-sulfonamide

Product 1

HCID 88239773benzyl (NE)-N-[[1-[1-(4-fluorophenyl)cyclobutyl]-7-[2-(propylsulfonylamino)ethoxy]-3,4-dihydro-1H-isoquinolin-2-yl]-(phenylmethoxycarbonylamino)methylidene]carbamate

Reagents, catalysts & solvents 2

HCID 76223Silver(I) trifluoromethanesulfonateCatalystHCID 6228DimethylformamideSolvent

Procedure

N-[2-({1-[1-(4-Fluorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}oxy)ethyl]propane-1-sulfonamide (100 mg, 0.224 mmol, cf. example 65) and dibenzyl [(methylsulfanyl)methylylidene]biscarbamate (104 mg, 0.291 mmol) were dissolved in dry dimethylformamide (1 mL). Triethylamine (0.094 mL, 0.672 mmol) was added followed by silver trifluoromethanesulfonate (81 mg, 0.313 mmol). A yellow precipitate was formed and the reaction mixture turned dark brown. Stirring was continued at room temperature for 3 h. The solvent was evaporated in vacuo. Dichloromethane (15 mL) was added, the solid was removed by filtration and washed with dichloromethane. The combined dichloromethane phases were concentrated in vacuo and the crude product was purified by flash chromatography (silica, dichloromethane then dichlorometane:methanol=100:1). Yield: 100 mg (0.132 mmol, 59%).

Workup

  1. customA yellow precipitate was formed
  2. customThe solvent was evaporated in vacuo
  3. additionDichloromethane (15 mL) was added
  4. customthe solid was removed by filtration
  5. washwashed with dichloromethane
  6. concentrationThe combined dichloromethane phases were concentrated in vacuo
  7. customthe crude product was purified by flash chromatography (silica, dichloromethane

Sources & evidence

ORD record
ord-11dd08a0d9e3423a983b1295885af3ff
Source dataset
uspto-grants-2014_02
Patent number
US08653100B2

Reaction notes

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