Cyclohexanecarboxylic acid → 2-(7-Chloro-1,8-naphthyridin-2-yl)-3-(4-cyclohexylcarbonylpiperazin-1-yl)carbonyloxy-isoindolin-1-one

HRID 27079

Reaction equation

HRID 27079 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]([N:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)=[O:23])[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]3=[O:30])=[N:9]2)=[CH:4][CH:3]=1.C1(N=C=NC2CCCCC2)CCCCC1.[CH:46]1([C:52](O)=[O:53])[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1>C(Cl)Cl>[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]([N:24]4[CH2:25][CH2:26][N:27]([C:52]([CH:46]5[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]5)=[O:53])[CH2:28][CH2:29]4)=[O:23])[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]3=[O:30])=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7413Cyclohexanecarboxylic acidHCID 10868DicyclohexylcarbodiimideHCID 233436392-(7-Chloro-1,8-naphthyridin-2-yl)-3-(piperazin-1-yl)carbonyloxy-isoindolin-1-one

Product 1

HCID 137286392-(7-Chloro-1,8-naphthyridin-2-yl)-3-(4-cyclohexylcarbonylpiperazin-1-yl)carbonyloxy-isoindolin-1-oneYield 69.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The procedure of Example 14 is followed but starting with 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(piperazin-1-yl)carbonyloxy-isoindolin-1-one (4.23 g.), N,N'-dicyclohexylcarbodiimide (3.1 g.) in anhydrous methylene chloride (100 cc.) and cyclohexylcarboxylic acid (1.92 g.). After having filtered off the precipitate, the organic solution is washed with an 8% aqueous solution of sodium bicarbonate (20 cc.) and then dried over anhydrous potassium carbonate (10 g.). After the solution has been filtered and the filtrate concentrated to dryness, the residue is recrystallised from ethanol (300 cc.). 2-(7-Chloro-1,8-naphthyridin-2-yl)-3-(4-cyclohexylcarbonylpiperazin-1-yl)carbonyloxy-isoindolin-1-one (3.7 g.), which melts at 240° C., is thus obtained.

Workup

  1. filtrationAfter having filtered off the precipitate
  2. washthe organic solution is washed with an 8% aqueous solution of sodium bicarbonate (20 cc.)
  3. dry with materialdried over anhydrous potassium carbonate (10 g.)
  4. filtrationAfter the solution has been filtered
  5. concentrationthe filtrate concentrated to dryness
  6. customthe residue is recrystallised from ethanol (300 cc.)

Sources & evidence

ORD record
ord-33753e00e901425a81626c524cf476cf
Source dataset
uspto-grants-1980_09
Patent number
US04220646

Linked notes

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