Potassium Iodide → HCID 72514630, compound

HRID 1166785Notes

Reaction equation

HRID 1166785 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[OH:12])[C:5]([NH:7][NH2:8])=[O:6].Br[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[C:22]([O:27][CH3:28])[CH:23]=[CH:24][CH:25]=2)[C:20]([CH:29]=O)=[CH:19][CH:18]=1.C(OCC)(OCC)OCC.[I-].[K+].[CH2:43]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH2:46][CH2:45][NH:44]1>CN(C=O)C>[CH2:43]1[C:52]2[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH2:46][CH2:45][N:44]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[C:22]([O:27][CH3:28])[CH:23]=[CH:24][CH:25]=2)[C:20]([CH:29]=[N:8][NH:7][C:5](=[O:6])[C:4]2[CH:9]=[CH:10][C:11]([OH:12])=[C:2]([Cl:1])[CH:3]=2)=[CH:19][CH:18]=1

Participants

7

Reactant 5

HCID 4875Potassium IodideHCID 70461,2,3,4-TetrahydroisoquinolineHCID 31214Ethyl orthoformateHCID 109542683-Chloro-4-hydroxybenzohydrazideHCID 22999129HCID 22999129, compound

Product 1

HCID 72514630HCID 72514630, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The above resin bound 3-chloro-4-hydroxybenzoic acid hydrazide (2 g, 1.8 mmol) was swelled in DMF (25 mL) for 30 minutes and the above 4-(2-bromoethoxy)-8-methoxynaphthalene-1-carbaldehyde (1.7 g, 5.4 mmol) was added followed by triethyl orthoformate (1.2 mL) and the resulting mixture was shaken at room temperature for 16 hours. The mixture was filtered and the resin was successively washed with DMF (3×25 mL), dichloromethane (4×25 mL) and N-methyl pyrrolidin-2-one (NMP) (2×25 mL). NMP (25 mL) was added followed by potassium iodide (0.6 g) and 1,2,3,4-tetrahydro-isoquinoline (2.25 mL, 18 mmol) and the resulting mixture was shaken at room temperature for 16 hours. The mixture was filtered and the resin was successively washed with NMP (2×25 mL) and dichloromethane (6×25 mL). The compound was cleaved off the resin by addition of 50% TFA in dichloromethane (30 mL) and shaking at room temperature for 1 hour. After filtration followed by extraction of the resin with dichloromethane (2×30 mL) the combined filtrates were concentrated in vacuo. The residue was partitioned between ethyl acetate (80 mL) and saturated sodium hydrogen carbonate (100 mL). The aqueous phase was extracted with ethyl acetate (2×80 mL) and the combined organic extracts were dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (200 mL) eluting with a mixture of dichloromethane and methanol (9:1). This afforded 217 mg of the title compound.

Workup

  1. filtrationThe mixture was filtered
  2. washthe resin was successively washed with DMF (3×25 mL), dichloromethane (4×25 mL) and N-methyl pyrrolidin-2-one (NMP) (2×25 mL)
  3. additionNMP (25 mL) was added
  4. stirringthe resulting mixture was shaken at room temperature for 16 hours
  5. filtrationThe mixture was filtered
  6. washthe resin was successively washed with NMP (2×25 mL) and dichloromethane (6×25 mL)
  7. additionby addition of 50% TFA in dichloromethane (30 mL)
  8. stirringshaking at room temperature for 1 hour
  9. filtrationAfter filtration
  10. extractionfollowed by extraction of the resin with dichloromethane (2×30 mL) the combined filtrates
  11. concentrationwere concentrated in vacuo
  12. customThe residue was partitioned between ethyl acetate (80 mL) and saturated sodium hydrogen carbonate (100 mL)
  13. extractionThe aqueous phase was extracted with ethyl acetate (2×80 mL)
  14. dry with materialthe combined organic extracts were dried (MgSO4)
  15. concentrationconcentrated in vacuo
  16. customThe residue was purified by column chromatography on silica gel (200 mL)
  17. washeluting with a mixture of dichloromethane and methanol (9:1)

Sources & evidence

ORD record
ord-6580c722e5464abcb5d7876501d5a440
Source dataset
uspto-grants-2003_09
Patent number
US06613942B1

Reaction notes

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