Tetrahydrofuran → HCID 21422086, compound

HRID 328268Notes

Reaction equation

HRID 328268 reaction equation
[C:1]([C:3]1[N:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9]([N:13]3[CH:21]([OH:22])[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14]3=[O:23])=[N:10]2)=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].ClC([CH:29]1[CH2:34][N:33]([CH3:35])[CH2:32][CH2:31][NH:30]1)=O.[O:36]1CCC[CH2:37]1>C(Cl)Cl.CN(P(N(C)C)(N(C)C)=O)C>[C:1]([C:3]1[N:12]=[C:11]2[C:6]([CH:7]=[CH:8][C:9]([N:13]3[CH:21]([O:22][C:37]([N:30]4[CH2:29][CH2:34][N:33]([CH3:35])[CH2:32][CH2:31]4)=[O:36])[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14]3=[O:23])=[N:10]2)=[CH:5][CH:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 21422090HCID 21422090, compoundHCID 21444380HCID 21444380, compound

Product 1

HCID 21422086HCID 21422086, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

Following the procedure of Example 4 but starting with 2-(7-cyano-1,8-naphthyridin-2-yl)-3-hydroxy-isoindolin-1-one (4.7 g.), sodium hydride (50% dispersion in mineral oil) (1.5 g.), 2-chlorocarbonyl-4-methylpiperazine (5.04 g.), anhydrous tetrahydrofuran (97 cc.) and anhydrous hexamethylphosphotriamide (25 cc.), a crude product (5.7 g.) is obtained which is then dissolved in methylene chloride (100 cc.). The resulting solution is passed through a column of silica gel (57 g.). Elution is carried out successively with methylene chloride (2,400 cc.), ethyl acetate (1,400 cc.) and then a mixture (200 cc.) of ethyl acetate and methanol (50--50 by volume), collecting 200 cc. fractions. The last eight fractions are combined and concentrated to dryness. The residue, weighing 3.4 g., is recrystallised from acetonitrile (250 cc.) to yield 2-(7-cyano-1,8-naphthyridin-2-yl)-3-(4-methylpiperazin-1-yl)carbonyloxy-isoindolin-1-one (2.6 g.) melting at 266°-268° C.

Workup

  1. customa crude product (5.7 g.) is obtained which
  2. washElution
  3. customa mixture (200 cc.) of ethyl acetate and methanol (50--50 by volume), collecting 200 cc
  4. concentrationconcentrated to dryness
  5. custom, is recrystallised from acetonitrile (250 cc.)

Sources & evidence

ORD record
ord-efccb1c2942a413cbca502be5349e008
Source dataset
uspto-grants-1977_04
Patent number
US04016274

Reaction notes

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