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

HRID 1406889ノート

反応式

HRID 1406889 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-62bd7d7eaae74d318bd2449ff39b38f1
出典データセット
uspto-grants-2014_12
特許番号
US08916576B2

反応ノート

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