Pyridine → 5-[5-(tert-Butoxycarbonylamino-methyl)-2-chloro-benzoylamino]-2-[2-(methoxy)ethoxy]-benzoic acid

HRID 1846113Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1846113
ClC(N(C)C)=C(C)C.[C:9]([O:13][C:14]([NH:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]([Cl:27])=[C:22]([CH:26]=1)[C:23]([OH:25])=O)=[O:15])([CH3:12])([CH3:11])[CH3:10].N1C=CC=CC=1.C([O:36][C:37](=[O:50])[C:38]1[CH:43]=[C:42]([NH2:44])[CH:41]=[CH:40][C:39]=1[O:45][CH2:46][CH2:47][O:48][CH3:49])C>CC#N>[C:9]([O:13][C:14]([NH:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]([Cl:27])=[C:22]([CH:26]=1)[C:23]([NH:44][C:42]1[CH:41]=[CH:40][C:39]([O:45][CH2:46][CH2:47][O:48][CH3:49])=[C:38]([CH:43]=1)[C:37]([OH:50])=[O:36])=[O:25])=[O:15])([CH3:10])([CH3:11])[CH3:12]

Komponenten

6

Edukt 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 584833005-Amino-2-(2-methoxyethoxy)-benzoic acid ethyl esterHCID 584833575-(((tert-Butoxycarbonyl)amino)methyl)-2-chlorobenzoic acid

Produkt 1

HCID 671172405-[5-(tert-Butoxycarbonylamino-methyl)-2-chloro-benzoylamino]-2-[2-(methoxy)ethoxy]-benzoic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

1-Chloro-N,N,2-trimethylpropenylamine (166 μL; 1.25 mmol) was added to a mixture of 5-(tert-butoxycarbonylamino)methyl-2-chloro benzoic acid (263 mg; 0.92 mmol) in MeCN (10 mL) and stirred at rt for 15 min. Pyridine (198 μL; 2.51 mmol) and 5-amino-2-(2-methoxyethoxy)-benzoic acid ethyl ester (200 mg; 0.84 mmol) was added and it was stirred at rt overnight. The mixture was filtered through a pad of Alox B, washed with DMF/MeOH 9/1 and concentrated i. vac. The residue was mixed with 15 mL MeOH and 15 mL 2 M aq NaOH and stirred for 3 days at rt. After concentration, the residue was diluted with 10 mL 4M aq. HCl, extracted with EtOAc, dried with Na2SO4 and concentrated i. vac. The crude was mixed with 50 mL Dioxan; 5 mL H2O and di-tert-butyldicarbonate (200 mg), stirred at rt for 2 h and concentrated. Yield: 380 mg (95%); MS: [M+H]+=479 (Cl isotope pattern); HPLC: Rt=2.01 min (Method CC-4)

Aufarbeitung

  1. stirringit was stirred at rt overnight
  2. filtrationThe mixture was filtered through a pad of Alox B
  3. washwashed with DMF/MeOH 9/1
  4. concentrationconcentrated i
  5. additionThe residue was mixed with 15 mL MeOH and 15 mL 2 M aq NaOH
  6. stirringstirred for 3 days at rt
  7. concentrationAfter concentration
  8. additionthe residue was diluted with 10 mL 4M aq. HCl
  9. extractionextracted with EtOAc
  10. dry with materialdried with Na2SO4
  11. concentrationconcentrated i
  12. additionThe crude was mixed with 50 mL Dioxan
  13. stirring5 mL H2O and di-tert-butyldicarbonate (200 mg), stirred at rt for 2 h
  14. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-88a4bca7047a48e0a3d70338a43d477a
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08951999B2

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