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Triethylamine → (R)-{2-[3,5-Diethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazol-4-ylmethyl]-1,2,3,4-tetrahydroisoquinolin-3-yl}methanol

HRID 1740101
Notes
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Reaction equation

HRID 1740101 reaction equation
[CH2:1]([C:3]1[C:7]([CH2:8]O)=[C:6]([CH2:10][CH3:11])[N:5]([C:12]2[C:17]([CH3:18])=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=2[CH3:20])[N:4]=1)[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.[OH:33][CH2:34][CH:35]1[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:37][NH:36]1>C(Cl)Cl.C(#N)C.CN(C)C=O.O>[CH2:1]([C:3]1[C:7]([CH2:8][N:36]2[C@@H:35]([CH2:34][OH:33])[CH2:44][C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH2:37]2)=[C:6]([CH2:10][CH3:11])[N:5]([C:12]2[C:17]([CH3:18])=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=2[CH3:20])[N:4]=1)[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 3752277(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanolHCID 218373233,5-Diethyl-1-(2,4,6-trimethylphenyl)pyrazole-4-methanol

Product 1

HCID 67553250(R)-{2-[3,5-Diethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazol-4-ylmethyl]-1,2,3,4-tetrahydroisoquinolin-3-yl}methanolYield 44.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21891449acetonitrile N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 272 mg (1,0 mmol) of 3,5-diethyl-1-(2,4,6-trimethylphenyl)pyrazole-4-methanol in 5 mL of methylene chloride cooled to 0° C. under dry nitrogen in a 25 mL 3-neck flask, was added to 0.2 mL (2.5 mmol) of triethylamine and 0.092 mL (2.0 mmol) of methanesulfonyl chloride. This mixture was stirred for 15 minutes at 0° C. and then 0.648 g (4.0 mmol) of (+)-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline in 1 mL of 50:50 dimethylformamide acetonitrile was added. The reaction mixture was heated at reflux overnight whereupon no starting material was seen by TLC. The cooled reaction mixture was diluted with water and the product was extracted with ethyl acetate. After drying (brine wash, magnesium sulfate) and evaporation, the crude product was chromatographed on silica gel, eluting with 10:1 and 5:1 hexane/ethyl acetate to give 184 mg (44%) of the desired product. 1H-NMR (CDCl3):0.80 (3H, t, J=7), 1.18 (3H, t, J=7), 1.92 (6H, s), 2.21 (2H, q, J=7), 2.28 (3H, s), 2.55 (2H, q, J=7), 2.97 (2H, d of d, J=7), 3.25 (1H, m), 3.50-3.66 (5H, m), 3.80 (2H, d, J=12), 6.82-7.16 (6H, m).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight whereupon no starting material
  3. customThe cooled reaction mixture
  4. extractionthe product was extracted with ethyl acetate
  5. customAfter drying
  6. wash(brine wash, magnesium sulfate) and evaporation
  7. customthe crude product was chromatographed on silica gel
  8. washeluting with 10:1 and 5:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-31ac6f64ce924e1683bcba94e1e69668
Source dataset
uspto-grants-1999_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05968944

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes