Diethylamine → 6-[(Diethylamino)methyl]-2-(trifluoromethyl)pyrimidine-4-carboxylic acid

HRID 1617407Notes

Reaction equation

HRID 1617407 reaction equation
Br[CH2:2][C:3]1[N:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[N:6]=[C:5]([C:13]([O:15]CC)=[O:14])[CH:4]=1.[CH2:18]([NH:20][CH2:21][CH3:22])[CH3:19].O.[OH-].[Li+]>C(Cl)Cl.O1CCCC1.O>[CH2:18]([N:20]([CH2:2][C:3]1[N:8]=[C:7]([C:9]([F:10])([F:11])[F:12])[N:6]=[C:5]([C:13]([OH:15])=[O:14])[CH:4]=1)[CH2:21][CH3:22])[CH3:19]

Participants

7

Reactant 3

HCID 8021DiethylamineHCID 168937Lithium hydroxide, monohydrateHCID 58431340Ethyl 6-(bromomethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate

Product 1

HCID 584314366-[(Diethylamino)methyl]-2-(trifluoromethyl)pyrimidine-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 6-(bromomethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate (0.15 g, 0.32 mmol, prepared as in Example 5, Step A) in methylene chloride (3.0 mL) was added N-ethylethanamine (0.13 mL, 1.3 mmol). After 30 minutes, the solvent was removed in vacuo. The ester was hydrolyzed by stirring with lithium hydroxide monohydrate (0.12 g, 3.0 mmol) in a mixture of tetrahydrofuran (5 mL) and water (2 mL). After 1 hour, 1N HCl was added dropwise to neutralize. Purification via preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) afforded product as a light yellow solid. Yield: 0.050 g (60%); LC-MS: 278.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 7.97 (s, 1H), 3.74 (s, 2H), 2.52 (q, 4H), 0.99 (t, 6H).

Workup

  1. customthe solvent was removed in vacuo
  2. waitAfter 1 hour
  3. customPurification via preparative HPLC-MS (C18
  4. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)
  5. customafforded product as a light yellow solid

Sources & evidence

ORD record
ord-f3bc2379c19646b692c3b24b4579d64b
Source dataset
uspto-grants-2014_07
Patent number
US08765734B2

Reaction notes

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