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

HRID 61546Notes

Reaction equation

HRID 61546 reaction equation
[C:1]([O:5][C:6]([C@@H:8]([CH3:12])[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.[NH2:55][C:56]1[CH:57]=[C:58]([C:62]2[N:71]=[C:70]([NH:72][C:73]3[CH:74]=[C:75]4[C:79](=[CH:80][CH:81]=3)[N:78]([C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[N:77]=[CH:76]4)[C:69]3[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=3)[N:63]=2)[CH:59]=[CH:60][CH:61]=1>C(Cl)Cl>[C:1]([O:5][C:6]([C@@H:8]([CH3:12])[C:9]([NH:55][C:56]1[CH:57]=[C:58]([C:62]2[N:71]=[C:70]([NH:72][C:73]3[CH:74]=[C:75]4[C:79](=[CH:80][CH:81]=3)[N:78]([C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[N:77]=[CH:76]4)[C:69]3[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=3)[N:63]=2)[CH:59]=[CH:60][CH:61]=1)=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 66825994tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylateHCID 86642405(S)-2-(tert-butoxycarbonyl)propanoic acid

Product 1

HCID 68789429tert-butyl 5-(2-(3-((S)-2-(tert-butoxycarbonyl)propanamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A suspension of (S)-2-(tert-butoxycarbonyl)propanoic acid (21 mg, 0.11 mmol), PyBOP® (57 mg, 0.11 mmol), DIEA (49 μL, 0.28 mmol) in CH2Cl2 (0.5 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 (100 mg, 0.22 mmol) and CH2Cl2 (1 mL). The reaction mixture was stirred at RT for 1.5 h. Activated another 0.5 equivalent of the acid as described above and it was once again added to the reaction mixture. Stirred for 16 h, diluted with more CH2Cl2 and extracted with H2O (3×). Organic layer was dried under Na2SO4 and concentrated in vacuo to give the desired product tert-butyl 5-(2-(3-((S)-2-(tert-butoxycarbonyl)propanamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate. (95 mg, 69%).

Workup

  1. stirringThe reaction mixture was stirred at RT for 1.5 h
  2. additionwas once again added to the reaction mixture
  3. stirringStirred for 16 h
  4. extractionextracted with H2O (3×)
  5. customOrganic layer was dried under Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e4c2d4d4c99441168915da97df08b124
Source dataset
uspto-grants-2016_09
Patent number
US09440961B2

Reaction notes

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