Dimethylamine → 6-[(Dimethylamino)methyl]-2-(trifluoromethyl)pyrimidine-4-carboxylic acid

HRID 1617402Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1617402
[CH3:1][NH:2][CH3:3].C1COCC1.Br[CH2:10][C:11]1[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:14]=[C:13]([C:21]([O:23]CC)=[O:22])[CH:12]=1.O.[OH-].[Li+]>C(Cl)Cl>[CH3:1][N:2]([CH2:10][C:11]1[N:16]=[C:15]([C:17]([F:20])([F:18])[F:19])[N:14]=[C:13]([C:21]([OH:23])=[O:22])[CH:12]=1)[CH3:3]

Komponenten

6

Edukt 4

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 58431340Ethyl 6-(bromomethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate

Produkt 1

HCID 584314096-[(Dimethylamino)methyl]-2-(trifluoromethyl)pyrimidine-4-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 2.0 M dimethylamine in THF (5.27 mL, 10.5 mmol) was added a solution of ethyl 6-(bromomethyl)-2-(trifluoromethyl)pyrimidine-4-carboxylate (0.33 g, 1.0 mmol, from Step A) in methylene chloride (5.0 mL). The reaction was stirred at room temperature for 2 hours, then concentrated. The residue was dissolved in tetrahydrofuran (20 mL), water (6 mL) was added, followed by lithium hydroxide monohydrate (0.4 g, 10 mmol). The mixture was stirred for one hour, then was rotovapped to remove most of the THF. The pH was adjusted to 7 by the addition of cone. HCl. Acetonitrile (10 mL) was added, the mixture was filtered and then purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) to afford product as a light yellow solid. Yield: 0.153 g (58%); LC-MS: 250.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 8.02 (s, 1H), 3.70 (s, 2H), 2.27 (s, 6H).

Aufarbeitung

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
  3. additionwater (6 mL) was added
  4. stirringThe mixture was stirred for one hour
  5. customto remove most of the THF
  6. additionThe pH was adjusted to 7 by the addition of cone
  7. additionAcetonitrile (10 mL) was added
  8. filtrationthe mixture was filtered
  9. custompurified via preparative HPLC-MS (C18
  10. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)
  11. customto afford product as a light yellow solid

Quellen und Nachweise

ORD-Eintrag
ord-dc08547dbc8c46449815698f78596669
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765734B2

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