Triphenylphosphine → 5-Chloro-N-(1,3-dioxo-2-{[1-(4-pyridinyl)-4-piperidinyl]methyl}-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide

HRID 1455678Notes

Reaction equation

HRID 1455678 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][CH:10]([CH2:13]O)[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[Cl:15][C:16]1[S:20][C:19]([C:21]([NH:23][C:24]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:25]=2[C:26](=[O:34])[NH:27][C:28]3=[O:33])=[O:22])=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Cl:15][C:16]1[S:20][C:19]([C:21]([NH:23][C:24]2[CH:32]=[CH:31][CH:30]=[C:29]3[C:25]=2[C:26](=[O:34])[N:27]([CH2:13][CH:10]2[CH2:9][CH2:8][N:7]([C:4]4[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=4)[CH2:12][CH2:11]2)[C:28]3=[O:33])=[O:22])=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 41357405-Chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)thiophene-2-carboxamideHCID 5462977Diethyl azodicarboxylateHCID 11310048(1-(Pyridin-4-YL)piperidin-4-YL)methanol

Product 1

HCID 184406835-Chloro-N-(1,3-dioxo-2-{[1-(4-pyridinyl)-4-piperidinyl]methyl}-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(4-Pyridyl)-4-piperidinemethanol (U.S. Pat. No. 4,968,704) (211.5 mg, 1.1 mmol), 5-chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide (306.7 mg, 1 mmol), triphenylphosphine (1049 mg, 4 mmol) are initially charged in 40 ml of THF, and diethylazodicarboxylate (DEAD) (696.6 mg, 4 mmol, 0.63 ml) is added. The mixture is stirred at room temperature overnight and then concentrated by evaporation, the residue is dissolved in ethanol, silica gel is added, the mixture is re-concentrated by evaporation and the residue is applied to a silica gel column. Elution with toluene/ethyl acetate and toluene/ethanol (25:1) mixtures gives a main fraction of Rf (SiO2, toluene/ethanol=4:1)=0.19. This fraction is evaporated and treated with ethanol, and the resulting crystals (112 mg, 23.3% of theory) are filtered off with suction. M.p.: 123° C. (decomp.).

Workup

  1. concentrationconcentrated by evaporation
  2. dissolutionthe residue is dissolved in ethanol
  3. additionsilica gel is added
  4. concentrationthe mixture is re-concentrated by evaporation
  5. washElution with toluene/ethyl acetate and toluene/ethanol (25:1)
  6. custommixtures gives a main fraction of Rf (SiO2, toluene/ethanol=4:1)=0.19
  7. customThis fraction is evaporated
  8. additiontreated with ethanol
  9. filtrationthe resulting crystals (112 mg, 23.3% of theory) are filtered off with suction

Sources & evidence

ORD record
ord-1324ed556bdc48aa9c57b7c33bfeffc4
Source dataset
uspto-grants-2009_01
Patent number
US07482472B2

Reaction notes

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