Triethylamine → {2-[5-Dimethylamino-3-methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazol-4-yl-methyl]-1,2,3,4-tetrahydro-isoquinolin-3-yl}-methanol

HRID 1378645Notes

Reaction equation

HRID 1378645 reaction equation
[CH3:1][N:2]([CH3:20])[C:3]1[N:7]([C:8]2[C:13]([Cl:14])=[CH:12][C:11]([Cl:15])=[CH:10][C:9]=2[Cl:16])[N:6]=[C:5]([CH3:17])[C:4]=1[CH2:18]O.C(N(CC)CC)C.CS(Cl)(=O)=O.S([O-])(=O)(=O)C.[OH:38][CH2:39][CH:40]1[CH2:49][C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42][NH:41]1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.C(OCC)(=O)C.O.C(#N)C.CN(C)C=O>[CH3:1][N:2]([CH3:20])[C:3]1[N:7]([C:8]2[C:13]([Cl:14])=[CH:12][C:11]([Cl:15])=[CH:10][C:9]=2[Cl:16])[N:6]=[C:5]([CH3:17])[C:4]=1[CH2:18][N:41]1[CH:40]([CH2:39][OH:38])[CH2:49][C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42]1

Participants

11

Reactant 6

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 3752277(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanolHCID 22911382[5-Dimethylamino-3-methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazol-4-yl]-methanol2×

Product 1

HCID 67690409{2-[5-Dimethylamino-3-methyl-1-(2,4,6-trichlorophenyl)-1H-pyrazol-4-yl-methyl]-1,2,3,4-tetrahydro-isoquinolin-3-yl}-methanol

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
5 °C

Procedure

To an ice-bath-chilled, well-stirred solution of the compound of Step C (160 mg, 0.48 mmol and triethylamine (0.08 ml, 0.60 mmol) in anhydrous methylene chloride (3 ml), methanesulfonyl chloride (0.04 ml, 59.2 mg, 0.52 mmol) was added all at once. After 15 minutes of stirring at 5° C. to complete in situ formation of the mesylate of the compound of Step C, the dextrorotatory enantiomer of 3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline (310 mg, 1.9 mmol), anhydrous N,N-dimethylformamide (0.51 ml) and acetonitrile (1.2 ml) were added. After stirring 1/2 hour at ambient temperature, the reaction mixture was heated at 55° C. for 19 hours. Concentration in vacuo afforded an orange residue which was dissolved in ethyl acetate/water (100 ml of each) with the pH adjusted to 10 with sodium carbonate. The separated aqueous phase was extracted twice with 50 ml portions of ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to an orange semi-solid (0.7 g). Flash chromatography of the entire sample (silica gel, 40 micron mesh; eluting with ethyl acetate/hexane=1.3 volume) afforded the title compound (170 mg) as a light-orange oil. 13C NMR (CDCl3): 151.6, 151.0, 136.2, 135.3, 135.0, 133.6, 133.3, 129.0, 128.6, 127.0, 126.5, 126.1, 107.5, 62.0, 58.0, 47.6, 45.6, 42.6, 26.2, 13.1.

Workup

  1. additionwas added all at once
  2. stirringAfter stirring 1/2 hour at ambient temperature
  3. temperaturethe reaction mixture was heated at 55° C. for 19 hours
  4. concentrationConcentration in vacuo
  5. customafforded an orange residue which
  6. extractionThe separated aqueous phase was extracted twice with 50 ml portions of ethyl acetate
  7. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo to an orange semi-solid (0.7 g)
  9. washFlash chromatography of the entire sample (silica gel, 40 micron mesh; eluting with ethyl acetate/hexane=1.3 volume)

Sources & evidence

ORD record
ord-f26c9c5b298345899862a09be2ae39cd
Source dataset
uspto-grants-1997_09
Patent number
US05668145

Reaction notes

Loading…