Triethylamine → 1-[3-(4-Fluorophenylthio)propyl]-4-(5-fluoro-2-pyrimidinyl) piperazine

HRID 981989Notes

Reaction equation

HRID 981989 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.Br[CH2:15][CH2:16][CH2:17][S:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1.C(N(CC)CC)C.[K+].[Br-]>CC#N>[F:25][C:22]1[CH:21]=[CH:20][C:19]([S:18][CH2:17][CH2:16][CH2:15][N:11]2[CH2:10][CH2:9][N:8]([C:5]3[N:6]=[CH:7][C:2]([F:1])=[CH:3][N:4]=3)[CH2:13][CH2:12]2)=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 253877Potassium BromideHCID 100581585-Fluoro-2-(piperazin-1-yl)pyrimidineHCID 14575314Benzene, 1-[(3-bromopropyl)thio]-4-fluoro-

Product 1

HCID 157298861-[3-(4-Fluorophenylthio)propyl]-4-(5-fluoro-2-pyrimidinyl) piperazine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
23 °C

Procedure

A mixture of 4-(5-fluoro-2-pyrimidinyl)piperazine (1.58 g, 8.67 mmol), 1-bromo-3-(4-fluorophenylthio)propane (2.16 g, 8.67 mmol), triethylamine (1.33 mL, 9.53 mmol) and KI (1.58 g, 9.52 mmol) in MeCN (45 mL) was refluxed under N2 atm. for 18 h, then cooled at 23° C. and concentrated under reduced pressure. The residue was solubilized in EtOAc (400 mL) and the resulting organic solution was washed with water (2×40 mL), dried (MgSO4) and concentrated to dryness. The crude material (3.0 g) was purified on a silica gel pad (3.4×8.5 cm) using a mixture of 50%-100% EtOAc in hexane. Appropriate fractions were combined and concentrated leaving 2.64 g (87%) mp 68°-70° C. Recrystallization from EtOH afforded an analytical sample, mp 70°-1° C.; 1H NMR (CDCl3, 200 MHz) δ: 1.6-1.9 (m, 2H), 2.2-2.7 (m, 6H), 2.92 (t, J=7 Hz, 2H), 3.6-3.9 (m, 4H), 6.9-7.1 (m, 2H), 7.3-7.5 (m, 2H), 8.17 (s, 2H); IR (KBr) ν: 1609, 1552, 1500, 1490 cm-1 ;

Workup

  1. temperaturewas refluxed under N2 atm
  2. concentrationconcentrated under reduced pressure
  3. washthe resulting organic solution was washed with water (2×40 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated to dryness
  6. customThe crude material (3.0 g) was purified on a silica gel pad (3.4×8.5 cm)
  7. additiona mixture of 50%-100% EtOAc in hexane
  8. concentrationconcentrated
  9. customleaving 2.64 g (87%) mp 68°-70° C
  10. customRecrystallization from EtOH
  11. customafforded an analytical sample, mp 70°-1° C.

Sources & evidence

ORD record
ord-f675e54c6ad8453f82fc98b5ba1c7f48
Source dataset
uspto-grants-1991_02
Patent number
US04994460

Reaction notes

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