1-Methylpiperazine → 3-(4-Methylpiperazin-1-yl)carbonyloxy-5-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)isoindolin-1-one

HRID 328271Notes

Reaction equation

HRID 328271 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[CH:20]([O:21][C:22]([O:24]C4C=CC=CC=4)=O)[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([Cl:31])[CH:18]=4)[C:13]3=[O:32])=[N:9]2)=[CH:4][CH:3]=1.[CH3:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1>C(#N)C.C(Cl)Cl.C(OCC)(=O)C>[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([C:22]([O:21][CH:20]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([Cl:31])[CH:18]=3)[C:13](=[O:32])[N:12]2[C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[N:11][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:9]=2)=[O:24])[CH2:36][CH2:35]1

Participants

6

Reactant 2

HCID 531671-MethylpiperazineHCID 214221182-(7-Chloro-1,8-naphthyridin-2-yl)-3-phenoxycarbonyloxy-5-chloro-isoindolin-1-one

Product 1

HCID 214220803-(4-Methylpiperazin-1-yl)carbonyloxy-5-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)isoindolin-1-oneYield 59.2%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

The procedure of Example 11 is followed but starting with 2-(7-chloro-1,8-naphthyridin-2-yl)-5-chloro-3-phenoxycarbonyloxy-isoindolin-1-one (1.25 g.) and 4-methylpiperazine (1.07 g.) in acetonitrile (33 cc.) and stirring for 24 hours at a temperature of about 20° C. From the reaction mixture, the resulting precipitate is filtered off and washed successively with acetonitrile (6 cc.) and diethyl ether (6 cc.). The product obtained (0.93 g.) is dissolved in methylene chloride (35 cc.), and the solution passed through a column of silica gel (10 g.). Elution is carried out with methylene chloride (16 × 20 cc.); the corresponding eluates are discarded. Elution is then carried out with ethyl acetate (5 × 20 cc.); the corresponding eluates are combined and concentrated under reduced pressure. A crystalline residue (0.9 g.) is obtained and is suspended in ethyl acetate (20 cc.). The crystals are filtered off and dried to yield 3-(4-methylpiperazin-1-yl)carbonyloxy- 5-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)isoindolin-1-one (0.75 g.) melting at 255° C.

Workup

  1. filtrationFrom the reaction mixture, the resulting precipitate is filtered off
  2. washwashed successively with acetonitrile (6 cc.) and diethyl ether (6 cc.)
  3. customThe product obtained (0.93 g.)
  4. washElution
  5. washElution
  6. concentrationconcentrated under reduced pressure
  7. customA crystalline residue (0.9 g.) is obtained
  8. filtrationThe crystals are filtered off
  9. customdried

Sources & evidence

ORD record
ord-00ca0fabcba2426c92d6496c60d3bd3d
Source dataset
uspto-grants-1977_04
Patent number
US04016274

Reaction notes

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