Diisopropylethylamine → tert-butyl 5-(2-(3-(2-(tert-butoxycarbonyl)acetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

HRID 61536

Reaktionsgleichung

Reaktionsgleichung von HRID 61536
[C:1]([O:5][C:6]([CH2:8][C:9]([OH:11])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:54][C:55]1[CH:56]=[C:57]([C:61]2[N:70]=[C:69]([NH:71][C:72]3[CH:73]=[C:74]4[C:78](=[CH:79][CH:80]=3)[N:77]([C:81]([O:83][C:84]([CH3:87])([CH3:86])[CH3:85])=[O:82])[N:76]=[CH:75]4)[C:68]3[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=3)[N:62]=2)[CH:58]=[CH:59][CH:60]=1>C(Cl)Cl>[C:1]([O:5][C:6]([CH2:8][C:9]([NH:54][C:55]1[CH:56]=[C:57]([C:61]2[N:70]=[C:69]([NH:71][C:72]3[CH:73]=[C:74]4[C:78](=[CH:79][CH:80]=3)[N:77]([C:81]([O:83][C:84]([CH3:87])([CH3:86])[CH3:85])=[O:82])[N:76]=[CH:75]4)[C:68]3[C:63](=[CH:64][CH:65]=[CH:66][CH:67]=3)[N:62]=2)[CH:58]=[CH:59][CH:60]=1)=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 5458533-(Tert-butoxy)-3-oxopropanoic acidHCID 2724699PyBOPHCID 66825994tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Produkt 1

HCID 56949455tert-butyl 5-(2-(3-(2-(tert-butoxycarbonyl)acetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

A suspension of 2-(tert-butoxycarbonyl)acetic acid (21 mg, 0.11 mmol), PyBOP® (57 mg, 0.11 mmol), DIEA (38 μL, 0.22 mmol) in anhydrous CH2Cl2 (0.5 mL) was stirred at RT for 10 minutes. This solution of activated acid was added to a suspension of tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate (100 mg, 0.22 mmol) and anhydrous CH2Cl2 (1 mL). The reaction mixture was stirred at RT for 1 h. Activated and added another 0.5 equivalent of the acid as described above and stirred for 1 h. Activated and added another 0.3 equivalents of the acid as described above. Stirred for and additional hour and diluted with CH2Cl2. Extracted with H2O (3×) and the organic layer was dried under Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica (1:1 EtOAc:Hexanes) to give the desired product tert-butyl 5-(2-(3-(2-(tert-butoxycarbonyl)acetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate. (123 mg, 0.20 mmol, 90%).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at RT for 1 h
  2. stirringstirred for 1 h
  3. stirringStirred for and additional hour
  4. extractionExtracted with H2O (3×)
  5. customthe organic layer was dried under Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica (1:1 EtOAc:Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c5bb056e7f1d4fbc9a3976faa010c410
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440961B2

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