Diisopropylethylamine → Methyl-(2-methyl-pyrimidin-4-yl)-{2-[2-methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethyl}-amine

HRID 966380Notes

Reaction equation

HRID 966380 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)=[C:12]([CH3:24])[S:11][C:10]=2[CH:25]=1.Cl[C:27]1[CH:32]=[CH:31][N:30]=[C:29]([CH3:33])[N:28]=1.C(N(C(C)C)C(C)C)C>CN(C)C=O>[CH3:1][N:2]([C:27]1[CH:32]=[CH:31][N:30]=[C:29]([CH3:33])[N:28]=1)[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[C:13]([C:14]3[CH:15]=[CH:16][C:17]([C:20]([F:21])([F:22])[F:23])=[CH:18][CH:19]=3)=[C:12]([CH3:24])[S:11][C:10]=2[CH:25]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 4244474-Chloro-2-methylpyrimidineHCID 22313989Methyl-{2-[2-methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethyl}-amine

Product 1

HCID 10182864Methyl-(2-methyl-pyrimidin-4-yl)-{2-[2-methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethyl}-amineYield 74.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 40 mg (0.109 mmol) Methyl-{2-[2-methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethyl}-amine (example 51.1), 0.0211 g (0.164 mmol) of 4-chloro-2-methyl-pyrimidine [Ger. Offen. (1990), DE3905364 A1] and 0.038 ml (0.22 mmol) N-ethyl-diisopropylamine in 1 ml of N,N-dimethylformamide was stirred for 2 hours at 80° C. The reaction mixture was then cooled to room temperature, poured into 30 ml of ice-water and extracted 3 times with 10 ml of ether. The combined ether phases were washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue formed was chromatographed on silica gel with a 95:5:1 v/v/v mixture of dichloromethane, methanol and saturated aqueous ammonia as the eluent giving 37.3 mg (74.5%) Methyl-(2-methyl-pyrimidin-4-yl)-{2-[2-methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethyl}-amine as light brown solid, MS: 458 (MH+).

Workup

  1. extractionextracted 3 times with 10 ml of ether
  2. washThe combined ether phases were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue formed
  6. customwas chromatographed on silica gel with a 95:5:1 v/v/v mixture of dichloromethane, methanol and saturated aqueous ammonia as the eluent

Sources & evidence

ORD record
ord-fe7664d1a82d4b77a157f8a7877b836e
Source dataset
uspto-grants-2005_10
Patent number
US06951879B2

Reaction notes

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