Sodium Iodide → 1-(2-Thienyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]butanone

HRID 981991Notes

Reaction equation

HRID 981991 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.[CH:14]1[CH:18]=[C:17]([C:19]([CH2:21][CH2:22][CH2:23]Cl)=O)[S:16][CH:15]=1.C(N(CC)CC)C.[Na+].[I-].[K+].[Br-].CC(CC)=[O:38]>CCO>[S:16]1[CH:15]=[CH:14][CH:18]=[C:17]1[CH2:19][C:21](=[O:38])[CH2:22][CH2:23][N:11]1[CH2:10][CH2:9][N:8]([C:5]2[N:6]=[CH:7][C:2]([F:1])=[CH:3][N:4]=2)[CH2:13][CH2:12]1

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 6569Methyl Ethyl Ketone2×HCID 8471TriethylamineHCID 1235114-Chloro-1-(2-thienyl)butan-1-oneHCID 253877Potassium BromideHCID 100581585-Fluoro-2-(piperazin-1-yl)pyrimidine

Product 1

HCID 571277781-(2-Thienyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]butanone

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
23 °C

Procedure

To a hot (78° C.) mixture of 4-(5-fluoro-2-pyrimidinyl) piperazine (4.00 g, 22.0 mmol), 4-chloro-2'-butyrothienone (3.57 mL, 22.0 mmol) and triethylamine (6.97 mL, 50.0 mmol) in methylethyl ketone (125 mL) was added dropwise (1 h) a solution of NaI (4.8 g, 32.0 mmol) in methylethyl ketone (125 mL). The resulting mixture was refluxed for 22 h, then cooled at 23° C. and concentrated to dryness in vacuo. The residue was diluted with CH2Cl2 (400 mL) and the solution washed with aqueous NaOH solution (0.5N, 44 mL). Aqueous phase was separated and extracted with CH2Cl2 (2×10 mL). Organic extracts were combined, dried (MgSO4) and concentrated under reduced pressure to a crude material which was chromatographed on a silica gel column (5×16 cm) using a mixture 30-100% EtoAC in hexane. Appropriate fractions were combined and concentrated to afford a yellow solid, 2.0 g (27%). Recrystallization from Et2O gave an analytical sample, mp 77°-8° C. 1H NMR (CDCl3, 200 MHz) δ: 1.9-2.2 (m, CH2CH2CH2, 2H), 2.3-2.7 (m, 6H), 2.96 (t, J=7.0 Hz, COCH2, 2H), 3.6-3.9 (m, 4H), 7.0-7.2 (m, 1H), 7.5-7.7 (m, 1H), 7.7-7.8 (m, 1H), 8.18 (s, pyrimidinyl H, 2H); IR (KBr) ν: 1660, 1610, 1555, 1510, 1480, 1359 cm-1 ; UV (EtOH) λ: 248 (ε 19699), 284 (ε 6287 ). 330 (ε 1816).

Workup

  1. temperatureThe resulting mixture was refluxed for 22 h
  2. concentrationconcentrated to dryness in vacuo
  3. additionThe residue was diluted with CH2Cl2 (400 mL)
  4. washthe solution washed with aqueous NaOH solution (0.5N, 44 mL)
  5. customAqueous phase was separated
  6. extractionextracted with CH2Cl2 (2×10 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure to a crude material which
  9. customwas chromatographed on a silica gel column (5×16 cm)
  10. concentrationconcentrated
  11. customto afford a yellow solid, 2.0 g (27%)
  12. customRecrystallization from Et2O
  13. customgave an analytical sample, mp 77°-8° C

Sources & evidence

ORD record
ord-78f48ca332164bd8a6fc5ea23bb70c97
Source dataset
uspto-grants-1991_02
Patent number
US04994460

Reaction notes

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