Phthalimide → 2-[(4-[(6-Chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinyl)methyl]-1h-isoindole-1,3(2h)-dione

HRID 2086306Notes

Reaction equation

HRID 2086306 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]1(=[O:30])[NH:24][C:23](=[O:25])[C:22]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:21]12.N(C(OCC)=O)=NC(OCC)=O.Cl.[Cl:44][C:45]1[CH:46]=[C:47]2[C:52](=[CH:53][CH:54]=1)[CH:51]=[C:50]([S:55]([N:58]1[CH2:63][CH:62]([CH2:64]O)[N:61]([N:66]([CH3:79])[CH:67]3[CH2:72][CH2:71][N:70]([C:73]4[CH:78]=[CH:77][N:76]=[CH:75][CH:74]=4)[CH2:69][CH2:68]3)[C:60](=[O:80])[CH2:59]1)(=[O:57])=[O:56])[CH:49]=[CH:48]2>C(Cl)Cl>[Cl:44][C:45]1[CH:46]=[C:47]2[C:52](=[CH:53][CH:54]=1)[CH:51]=[C:50]([S:55]([N:58]1[CH2:59][C:60](=[O:80])[N:61]([N:66]([CH3:79])[CH:67]3[CH2:72][CH2:71][N:70]([C:73]4[CH:74]=[CH:75][N:76]=[CH:77][CH:78]=4)[CH2:69][CH2:68]3)[CH:62]([CH2:64][N:24]3[C:20](=[O:30])[C:21]4[C:22](=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:23]3=[O:25])[CH2:63]1)(=[O:57])=[O:56])[CH:49]=[CH:48]2

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 227272524-[(6-Chloro-2-naphthyl)sulfonyl]-6-(hydoxymethyl)-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-2-piperazinone hydrochloride

Product 1

HCID 227273052-[(4-[(6-Chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinyl)methyl]-1h-isoindole-1,3(2h)-dioneYield 89.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of triphenylphosphine (0.49 g), phthalimide (0.29 g) and methylene chloride (15 ml) was combined with diethyl azodicarboxylate (0.29 ml) with stirring at 0° C., and stirred for 10 minutes. This solution was combined, at 0° C. with stirring, with a solution of 4-[(6-chloro-2-naphthyl)sulfonyl]-6-(hydoxymethyl)-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-2-piperazinone hydrochloride (0.27 g) in methylene chloride (10 ml) and stirred at room temperature for 1 hour. The reaction mixture was washed with saturated aqueous sodium bicarbonate, dried, and concentrated under reduced pressure. The residue was purified by a column chromatography on a silica gel (dichloromethane: 10% aqueous ammonia-containing methanol=10:1) to obtain 2-[(4-[(6-chloro-2-naphthyl)sulfonyl]-1-[methyl[1-(4-pyridinyl)-4-piperidinyl]amino]-6-oxo-2-piperazinyl)methyl]-1H-isoindole-1,3(2H)-dione (0.28 g) as a pale yellow powder.

Workup

  1. stirringstirred for 10 minutes
  2. customwas combined, at 0° C.
  3. stirringstirred at room temperature for 1 hour
  4. washThe reaction mixture was washed with saturated aqueous sodium bicarbonate
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by a column chromatography on a silica gel (dichloromethane: 10% aqueous ammonia-containing methanol=10:1)

Sources & evidence

ORD record
ord-d9a5f828b1f24fd09bfdbb5563457a7f
Source dataset
uspto-grants-2004_04
Patent number
US06723722B1

Reaction notes

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