Sodium Iodide → 3-[2-[4-(4-Fluorobenzoyl)piperidin-1-yl]ethyl]thieno[3,4-d]pyrimidine-2,4-dione

HRID 1762827Notes

Reaction equation

HRID 1762827 reaction equation
[C:1]([C:5]1[C:9]([NH:10][C:11]([NH:13][CH2:14][CH2:15]Cl)=[O:12])=[CH:8][S:7][CH:6]=1)([O:3]C)=O.Cl.[F:18][C:19]1[CH:32]=[CH:31][C:22]([C:23]([CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[O:24])=[CH:21][CH:20]=1.C(=O)(O)[O-].[Na+].[I-].[Na+]>C(O)(C)C.O>[F:18][C:19]1[CH:20]=[CH:21][C:22]([C:23]([CH:25]2[CH2:30][CH2:29][N:28]([CH2:15][CH2:14][N:13]3[C:1](=[O:3])[C:5]4=[CH:6][S:7][CH:8]=[C:9]4[NH:10][C:11]3=[O:12])[CH2:27][CH2:26]2)=[O:24])=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 13911227N-(3-carbomethoxythien-4-yl)-N'-(2-chloroethyl)urea

Product 1

HCID 145003983-[2-[4-(4-Fluorobenzoyl)piperidin-1-yl]ethyl]thieno[3,4-d]pyrimidine-2,4-dioneYield 7.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

N-(3-Carbomethoxythien-4-yl)-N'-(chloroethyl)urea (U.S. Pat. No. 4,670,560) (5.24 g, 20 mmol) was dissolved in isopropanol (100 ml) and treated successively with 4-(4-fluorobenzoyl)piperidine hydrochloride (9.71 g, 40 mmol), sodium bicarbonate (3.7 g, 44 mmol) and sodium iodide (1.90 g, 12 mmol) and the mixture was heated to reflux under a nitrogen atmosphere for 12 hours. The reaction mixture was reduced to half volume, diluted with water, and concentrated to remove the remainder of the alcohol solvent. The residue was extracted with methylene chloride and the combined organic extracts were dried with saturated brine and magnesium sulfate. After concentration of the extracts, the residue was purified on silica gel using methylene chloride/ethanol/ammonium hydroxide (96:3.5:0.5) as eluant. The title compound was recrystallized from ethanol to give 0.598 g (7.4% yield) of beige crystals, mp 208°-215° C. (dec). IR(KBr): 1707, 1672, 1159, 1033, 974, 860, 835, 766, 671 and 460 cm-1 ; MS (DCI), 402 m/z (MH+); 1H NMR (DMSO-d6): δ 1.5-1.7 (m, 4 H), 2.1 (br t, J=7 Hz, 2H), 2.9 (br d, 2H), 3.2-3.55 (m, 3H), 3.9 (t, J=6.2 Hz, 2H), 6.8 (d, J=4 Hz, 1H), 7.3 (t, J=9 Hz, 2H), 8.0 (dd, H=5.8 Hz, 2H), 8.2 (d, J=4 Hz, 1H) and 11.5 (br s, 1H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux under a nitrogen atmosphere for 12 hours
  3. concentrationconcentrated
  4. customto remove the remainder of the alcohol solvent
  5. extractionThe residue was extracted with methylene chloride
  6. dry with materialthe combined organic extracts were dried with saturated brine and magnesium sulfate
  7. customAfter concentration of the extracts, the residue was purified on silica gel
  8. customThe title compound was recrystallized from ethanol

Sources & evidence

ORD record
ord-7631ad0ace4f43cea16f6a4f692d524c
Source dataset
uspto-grants-1989_05
Patent number
US04835157

Reaction notes

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