N-Methylethylamine → 6-{[Ethyl(methyl)amino]methyl}-2-(trifluoromethyl)pyrimidine-4-carboxylic acid

HRID 1617409Notes

Reaction equation

HRID 1617409 reaction equation
[CH3:1][NH:2][CH2:3][CH3:4].Br[CH2:6][C:7]1[N:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:10]=[C:9]([C:17]([O:19]CC)=[O:18])[CH:8]=1.O.[OH-].[Li+]>C(Cl)Cl.O1CCCC1.O>[CH2:3]([N:2]([CH2:6][C:7]1[N:12]=[C:11]([C:13]([F:16])([F:14])[F:15])[N:10]=[C:9]([C:17]([OH:19])=[O:18])[CH:8]=1)[CH3:1])[CH3:4]

Participants

7

Reactant 3

HCID 12219N-MethylethylamineHCID 168937Lithium hydroxide, monohydrateHCID 58431340Ethyl 6-(bromomethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate

Product 1

HCID 584312966-{[Ethyl(methyl)amino]methyl}-2-(trifluoromethyl)pyrimidine-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-methylethanamine (96 μL, 1.1 mmol) was added to a solution of ethyl 6-(bromomethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate (0.13 g, 0.28 mmol, prepared as in Example 5, Step A) in methylene chloride (2.6 mL). After stirring for 30 minutes, solvent was removed in vacuo. The ester was hydrolyzed by stirring with lithium hydroxide monohydrate (0.12 g, 2.8 mmol) in tetrahydrofuran (4 mL) and water (2 mL) for 1 hour. 1N HCl was added dropwise to adjust the pH to 7. Purification via preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) afforded product. Yield: 0.043 g (58%); LC-MS: 264.1 (M+H)+. 1H NMR (300 MHz, DMSO-d6): δ 8.03 (s, 1H), 3.75 (s, 2H), 2.51 (q, 2H), 2.22 (s, 3H), 1.05 (t, 3H).

Workup

  1. customsolvent was removed in vacuo
  2. customPurification via preparative HPLC-MS (C18
  3. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)
  4. customafforded product

Sources & evidence

ORD record
ord-0fa9a672a22d4579830457aa4627e3c4
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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