Hydrochloric Acid → 2-chloro-N4-(4-n-butyloxyphenyl)-5-fluoro-4-pyrimidineamine

HRID 76400

Reaction equation

HRID 76400 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[CH2:10]([O:14][C:15]1[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=1)[CH2:11][CH2:12][CH3:13].Cl.[OH-].[Na+]>CC(C)=O.O>[Cl:1][C:2]1[N:7]=[C:6]([NH:19][C:18]2[CH:17]=[CH:16][C:15]([O:14][CH2:10][CH2:11][CH2:12][CH3:13])=[CH:21][CH:20]=2)[C:5]([F:9])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 203524-ButyloxyanilineHCID 2507052,4-Dichloro-5-fluoropyrimidine

Product 1

HCID 220610772-chloro-N4-(4-n-butyloxyphenyl)-5-fluoro-4-pyrimidineamineYield 80%

Reagents, catalysts & solvents 1

HCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

To a solution of 2,4-dichloro-5-fluoropyrimidine (0.5 g, 3.0 mmol) and 4-n-butoxyaniline (0.49 g, 3 mmol) in acetone/H2O (1:9 mL) at room temperature was added concentrated HCl (0.1 mL). The mixture was heated at reflux for 1 h, cooled to room temperature, and made basic with 2 N NaOH (2 mL). The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude black solid was purified by chromatography (4:1 hexanes/EtOAc) to afford 2-chloro-N4-(4-n-butyloxyphenyl)-5-fluoro-4-pyrimidineamine (0.71 g, 80%) as a brown oil: 1H NMR (300 MHz, CDCl3) δ 8.01 (d, J=2.7 Hz, 1H), 7.51-7.46 (m, 2H), 6.95-6.89 (m, 2H), 6.83 (bs, 1H), 3.99-3.95 (t, J=6.5 Hz, 2H), 1.82-1.57 (m, 2H), 1.53-1.43 (m, 2H), 0.98 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1 h
  3. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  4. dry with materialthe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude black solid was purified by chromatography (4:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-7e9ea5e537f146b9b094a62a2caec0e0
Source dataset
uspto-grants-2014_09
Patent number
US08835430B2

Linked notes

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