Tetrahydrofuran → HCID 11762499, compound

HRID 1635059Notes

Reaction equation

HRID 1635059 reaction equation
[H-].[Na+].NC1C(Cl)=[CH:29][C:7]([C:8](OCC2CCN(CCCOC3C=CC(F)=CC=3)CC2)=O)=[C:6](OC)[CH:5]=1.[C:34]([N:41]1[CH:45]=[CH:44][N:43]=[CH:42]1)([N:36]1[CH:40]=[CH:39][N:38]=[CH:37]1)=O.[NH2:46][C:47]1[C:52]2[CH2:53][C:54]([CH3:57])([CH3:56])[O:55][C:51]=2[C:50]([C:58]([OH:60])=[O:59])=[CH:49][C:48]=1[Cl:61].[CH2:62]1COCC1>C(#N)C>[NH2:46][C:47]1[C:52]2[CH2:53][C:54]([CH3:57])([CH3:56])[O:55][C:51]=2[C:50]([C:58]([O:60][CH2:8][CH:7]2[CH2:29][CH2:42][N:43]([CH2:44][CH2:45][NH:41][C:34]3[C:37]([CH3:62])=[N:38][CH:39]=[CH:40][N:36]=3)[CH2:5][CH2:6]2)=[O:59])=[CH:49][C:48]=1[Cl:61]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 106577584-Amino-5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxylic acidHCID 22662758HCID 22662758, compound

Product 1

HCID 11762499HCID 11762499, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Sodium hydride (0.4 g) was added to a solution of intermediate 1 (2.3 g) in THF (65 ml). The mixture was stirred and refluxed for 3 hours, then cooled (solution I). 1,1′-Carbonylbis-1H-imidazole (1.65 g) was added to a solution of 4-amino-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxylic acid (2.42 g) in ACN (65 ml), stirred at room temperature. This mixture was stirred for 2 hours at room temperature. The solvent was evaporated. The residue was dissolved in THF (65 ml) (solution II). At room temperature, solution (II) was poured out into solution (I) and the reaction mixture was stirred for 90 minutes at room temperature. The solvent was evaporated. The residue was partitioned between DCM and water. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue was solidified in DIPE. The precipitate was filtered off and dried vacuum; 50° C.), yielding 1.58 g (33%) [1-[2-[(3-methyl-2-pyrazinyl)amino]ethyl]-4-piperidinyl]methyl 4-amino-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxylate (compound 6).

Workup

  1. temperaturerefluxed for 3 hours
  2. stirringstirred at room temperature
  3. stirringThis mixture was stirred for 2 hours at room temperature
  4. customThe solvent was evaporated
  5. dissolutionThe residue was dissolved in THF (65 ml) (solution II)
  6. additionAt room temperature, solution (II) was poured out into solution (I)
  7. stirringthe reaction mixture was stirred for 90 minutes at room temperature
  8. customThe solvent was evaporated
  9. customThe residue was partitioned between DCM and water
  10. customThe organic layer was separated
  11. customdried
  12. filtrationfiltered
  13. customthe solvent was evaporated
  14. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5)
  15. customThe pure fractions were collected
  16. customthe solvent was evaporated
  17. filtrationThe precipitate was filtered off
  18. customdried vacuum

Sources & evidence

ORD record
ord-60defa69cb044d479c333e02a325dad9
Source dataset
uspto-grants-2003_01
Patent number
US06509339B2

Reaction notes

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