Pyridine → HCID 9880105, compound

HRID 1837613Notes

Reaction equation

HRID 1837613 reaction equation
[C:1]([OH:12])(=O)[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.C(N=C=NC(C)C)(C)C.[OH:22][N:23]1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.FC(F)(F)C(OC1C(F)=C(F)C(F)=C(F)C=1F)=O.N1C=CC=CC=1.[C:65]1([CH2:75][NH2:76])[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[CH:68]=[CH:67][CH:66]=1>CN(C=O)C>[OH:22][NH:23][C:6](=[O:8])[C:5]1[CH:4]=[CH:3][C:2]([C:1]([NH:76][CH2:75][C:65]2[C:74]3[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=3)[CH:68]=[CH:67][CH:66]=2)=[O:12])=[CH:10][CH:9]=1

Participants

9

Reactant 7

HCID 1049Pyridine2×HCID 7489Terephthalic AcidHCID 83551-NaphthalenemethanamineHCID 12734DiisopropylcarbodiimideHCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine2×HCID 4327891Pentafluorophenyl Trifluoroacetate2×

Product 1

HCID 9880105HCID 9880105, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1 eq of Wang-O—NH2 is shaken with 11 eq of terephthalic acid, 5.5 eq N,N′-diisopropylcarbodiimide, 5.5 eq 1-hydroxybenzotriazole and 25 eq diisopropylethylamine in DMF for 4 h at 25° C. After that, the resin is washed with DMF (5 times), MeOH (3 times), THF (3 times), CH2Cl2 (3 times) and diethylether (3 times). The resin is then shaken with 5 eq pentafluorophenyl trifluoroacetate and 10 eq pyridine. After that, the resin is washed with DMF (2 times), followed by CH2Cl2 (2 times), followed by diethylether (2 times). The resin is then shaken with 5 eq of naphtalenemethylamine, 10 eq of diisopropylethylamine and leq of 1-hydroxybenzotriazole. It is then shaken with 5 eq pentafluorophenyl trifluoroacetate and 10 eq pyridine. After that, the resin is washed with DMF (2 times), followed by CH2Cl2 (2 times). To liberate the product from the solid support, the resin is shaken with 50% TFA in dry CH2Cl2 with 5% triisopropylsilane added at rt for 1 h. The liquid phase is filtered, the resin washed with CH2Cl2 (3 times), and the combined filtrates are evaporated. The crude product is dissolved in tert-butanol/H2O (80:20) and freeze-dried. To neutralize any remaining TFA, 100 μL of a 25% NH4OH-sol is added and freeze-dried, again. The remaining solid is purified by preparative LC-MS to N-hydroxy-N′-naphthalen-1-ylmethyl-terephthalamide, MS (APCI): 321.1 (M+1)

Workup

  1. washAfter that, the resin is washed with DMF (5 times), MeOH (3 times), THF (3 times), CH2Cl2 (3 times) and diethylether (3 times)
  2. washAfter that, the resin is washed with DMF (2 times)
  3. washAfter that, the resin is washed with DMF (2 times)
  4. additionadded at rt for 1 h
  5. filtrationThe liquid phase is filtered
  6. washthe resin washed with CH2Cl2 (3 times)
  7. customthe combined filtrates are evaporated
  8. dissolutionThe crude product is dissolved in tert-butanol/H2O (80:20)
  9. customfreeze-dried
  10. additionis added
  11. customfreeze-dried
  12. customThe remaining solid is purified by preparative LC-MS to N-hydroxy-N′-naphthalen-1-ylmethyl-terephthalamide, MS (APCI)

Sources & evidence

ORD record
ord-c4a70506b5fb4cf5b6ea2c2315f0304b
Source dataset
uspto-grants-2004_08
Patent number
US06784173B2

Reaction notes

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