N,N-Dimethylglycine → tert-butyl 5-(2-(3-(2-(dimethylamino)acetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

HRID 1808400Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1808400
[CH3:1][N:2]([CH3:7])[CH2:3][C:4](O)=[O:5].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:50][C:51]1[CH:52]=[C:53]([C:57]2[N:66]=[C:65]([NH:67][C:68]3[CH:69]=[C:70]4[C:74](=[CH:75][CH:76]=3)[N:73]([C:77]([O:79][C:80]([CH3:83])([CH3:82])[CH3:81])=[O:78])[N:72]=[CH:71]4)[C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[N:58]=2)[CH:54]=[CH:55][CH:56]=1>C(Cl)Cl>[CH3:1][N:2]([CH3:7])[CH2:3][C:4]([NH:50][C:51]1[CH:52]=[C:53]([C:57]2[N:66]=[C:65]([NH:67][C:68]3[CH:69]=[C:70]4[C:74](=[CH:75][CH:76]=3)[N:73]([C:77]([O:79][C:80]([CH3:83])([CH3:82])[CH3:81])=[O:78])[N:72]=[CH:71]4)[C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[N:58]=2)[CH:54]=[CH:55][CH:56]=1)=[O:5]

Komponenten

6

Edukt 4

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 66825994tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Produkt 1

HCID 59361935tert-butyl 5-(2-(3-(2-(dimethylamino)acetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

A suspension of 2-(dimethylamino)acetic acid (57 mg, 0.55 mmol), PyBOP® (286 mg, 0.55 mmol), DIEA (240 μL, 1.38 mmol) in CH2Cl2 (2 mL) was stirred at RT for 10-15 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 (500 mg, 1.10 mmol) and CH2Cl2 (4 mL). The reaction mixture was stirred at RT for 1.5 h. Activated another 1.5 equivalent of the acid as described above and stirred for 16 h. Diluted with more CH2Cl2 and extracted with H2O (3×). Organic layer was dried under Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica (9:1 CH2Cl2:MeOH) to give the desired product tert-butyl 5-(2-(3-(2-(dimethylamino)acetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate. (570 mg, 1.06 mmol, 96%).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at RT for 1.5 h
  2. stirringstirred for 16 h
  3. extractionextracted with H2O (3×)
  4. customOrganic layer was dried under Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica (9:1 CH2Cl2:MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-59625bea9bcd4023a0ca57884b1f7dab
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08357693B2

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