Ethylene Oxide → 1-[[1-[(2-Chlorophenyl)methyl]-3,5-dimethylpyrazol-4-yl]methyl-methylamino]-3-(4-ethoxyphenoxy)propan-2-ol

HRID 238123Notes

Reaction equation

HRID 238123 reaction equation
[CH2:1]([O:3][C:4]1[CH:14]=[CH:13][C:7]([O:8][CH2:9][CH:10]2[CH2:12][O:11]2)=[CH:6][CH:5]=1)[CH3:2].[Cl:15][C:16]1[CH:32]=[CH:31][CH:30]=[CH:29][C:17]=1[CH2:18][N:19]1[C:23]([CH3:24])=[C:22]([CH2:25][NH:26][CH3:27])[C:21]([CH3:28])=[N:20]1.O1CC1>CO>[Cl:15][C:16]1[CH:32]=[CH:31][CH:30]=[CH:29][C:17]=1[CH2:18][N:19]1[C:23]([CH3:24])=[C:22]([CH2:25][N:26]([CH3:27])[CH2:12][CH:10]([OH:11])[CH2:9][O:8][C:7]2[CH:13]=[CH:14][C:4]([O:3][CH2:1][CH3:2])=[CH:5][CH:6]=2)[C:21]([CH3:28])=[N:20]1

Participants

5

Reactant 3

HCID 6354Ethylene OxideHCID 2466725({1-[(2-chlorophenyl)methyl]-3,5-dimethyl-1H-pyrazol-4-yl}methyl)(methyl)amineHCID 37440512-[(4-Ethoxyphenoxy)methyl]oxirane

Product 1

HCID 48408151-[[1-[(2-Chlorophenyl)methyl]-3,5-dimethylpyrazol-4-yl]methyl-methylamino]-3-(4-ethoxyphenoxy)propan-2-olYield 63%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
68 °C

Procedure

2-((4-Ethoxyphenoxy)methyl)oxirane (0.06 g, 0.32 mmol) and 1-(1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-N-methylmethanamine (0.10 g, 0.38 mmol) were dissolved in methanol (0.32 ml), warmed to 68° C. and stirred until the oxirane was consumed as observed by TLC. The solution was cooled to room temperature and the solvent removed under reduced pressure. The resulting oil was purified using flash column chromatography with 1:2:0.01 ethyl acetate:hexanes:triethylamine as the eluting solvent to yield 0.09 g (63%) of 1-(((1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)methyl)(methyl)amino)-3-(4-ethoxyphenoxy)propan-2-ol as a clear liquid. 1H NMR (500 MHz, CDCl3) δ 7.35 (dd, J=7.8, 1.2, 1H), 7.17 (td, J=7.7, 1.3, 1H), 7.12 (td, J=7.5, 1.2, 1H), 6.85-6.79 (m, 4H), 6.48 (dd, J=7.6, 0.9, 1H), 5.28 (s, 2H), 4.12-4.04 (m, 1H), 3.97 (q, J=7.0, 2H), 3.90 (d, J=4.9, 2H), 3.47 (d, J=13.2, 1H), 3.34-3.29 (m, 1H), 2.60 (dd, J=12.2, 9.7, 1H), 2.48 (dq, J=12.2, 3.9, 1H), 2.26 (s, 3H), 2.24 (s, 3H), 2.11 (s, 3H), 1.38 (t, J=9.1, 3H). 13C NMR (75 MHz, CDCl3) δ 153.47, 153.04, 148.04, 138.67, 135.31, 131.92, 129.43, 128.79, 127.58, 127.50, 115.63, 115.63, 115.53, 115.53, 113.71, 71.25, 66.37, 64.14, 59.51, 51.70, 50.28, 42.09, 15.13, 12.36, 9.82. HRMS (m/z): [MNa]+ calc for C25H32ClN3O3Na+, 480.20. found 480.2030.

Workup

  1. customwas consumed
  2. temperatureThe solution was cooled to room temperature
  3. customthe solvent removed under reduced pressure
  4. customThe resulting oil was purified

Sources & evidence

ORD record
ord-c0b709bffacd439ea0f315b5ec4a0a39
Source dataset
uspto-grants-2014_02
Patent number
US08642614B2

Reaction notes

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