HCID 54107605, compound → HCID 54436221, compound

HRID 1166786Notes

Reaction equation

HRID 1166786 reaction equation
O[CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH:13]=[N:14][NH:15][C:16](=[O:25])[C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([Cl:24])[CH:18]=2)=[CH:5][CH:4]=1>C(Cl)Cl>[CH2:13]([NH:14][CH2:2][C:3]1[C:8]2[C:7](=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:6]([CH:13]=[N:14][NH:15][C:16](=[O:25])[C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[C:19]([Cl:24])[CH:18]=2)=[CH:5][CH:4]=1)[CH:6]([CH3:7])[CH3:5]

Participants

3

Reactant 1

HCID 54107605HCID 54107605, compound

Product 1

HCID 54436221HCID 54436221, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The resin bound 3-chloro-4-hydroxybenzoic acid (4-hydroxymethylnaphthylmethylene)hydrazide (Resin—[Building block 1]—[Building block 2]) (50 mg, ˜0.05 mmoles) was swelled in CH2Cl2 (1 mL) for 15 min, then washed with CH2Cl2(2×0.5 mL). 0.4 mL CH2Cl2 and 0.4 mL diisopropylethylamine was subsequently added and the suspension was cooled to 0° C. Methanesulfonylchloride (0.1 mL) was dissolved in CH2Cl2 (0.3 mL) and added to the suspension. The mixture was allowed to react at 0° C. for 30 min, then at 25° C. for 1 hour. The resin was isolated by filtration and washed with CH2Cl2 (2×0.5 mL) and DMSO (0.5 mL). DMSO (0.5 mL) was added followed by 50 μL isobutylamine and 100 μL diisopropylethylamine. The mixture was shaken at 25° C. for 16 hours, filtered and washed successively with DMSO (2×0.5 mL), THF (3×0.5 mL), CH3OH (0.5 mL), CH2Cl2 (0.5 mL), CH3OH (0.5 mL), CH2Cl2 (4×0.5 mL). The compound was cleaved from the resin by shaking for 1 hour at 25° C. with a 50% solution of trifluoroacetic acid in CH2Cl2 (1 mL). The mixture was filtered and the resin was extracted with acetonitrile (1 mL). The combined extracts were concentrated in vacuo. The residue was redissolved in a mixture of CH3OH (0.5 mL) and acetonitrile (0.5 mL) and concentrated in vacuo to give the title compound

Workup

  1. washwashed with CH2Cl2(2×0.5 mL)
  2. addition0.4 mL CH2Cl2 and 0.4 mL diisopropylethylamine was subsequently added
  3. dissolutionMethanesulfonylchloride (0.1 mL) was dissolved in CH2Cl2 (0.3 mL)
  4. additionadded to the suspension
  5. customto react at 0° C. for 30 min
  6. customThe resin was isolated by filtration
  7. washwashed with CH2Cl2 (2×0.5 mL) and DMSO (0.5 mL)
  8. additionDMSO (0.5 mL) was added
  9. filtrationfiltered
  10. washwashed successively with DMSO (2×0.5 mL), THF (3×0.5 mL), CH3OH (0.5 mL), CH2Cl2 (0.5 mL), CH3OH (0.5 mL), CH2Cl2 (4×0.5 mL)
  11. stirringby shaking for 1 hour at 25° C. with a 50% solution of trifluoroacetic acid in CH2Cl2 (1 mL)
  12. filtrationThe mixture was filtered
  13. extractionthe resin was extracted with acetonitrile (1 mL)
  14. concentrationThe combined extracts were concentrated in vacuo
  15. dissolutionThe residue was redissolved in a mixture of CH3OH (0.5 mL) and acetonitrile (0.5 mL)
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-26d935b3266e4c13b530b703d930e8a1
Source dataset
uspto-grants-2003_09
Patent number
US06613942B1

Reaction notes

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