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

HRID 1808409Notes

Reaction equation

HRID 1808409 reaction equation
O.[CH3:2][N:3]1[CH2:7][CH2:6][CH2:5][C@H:4]1[C:8]([OH:10])=O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:53][C:54]1[CH:55]=[C:56]([C:60]2[N:69]=[C:68]([NH:70][C:71]3[CH:72]=[C:73]4[C:77](=[CH:78][CH:79]=3)[N:76]([C:80]([O:82][C:83]([CH3:86])([CH3:85])[CH3:84])=[O:81])[N:75]=[CH:74]4)[C:67]3[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=3)[N:61]=2)[CH:57]=[CH:58][CH:59]=1>C(Cl)Cl>[CH3:2][N:3]1[CH2:7][CH2:6][CH2:5][C@H:4]1[C:8]([NH:53][C:54]1[CH:55]=[C:56]([C:60]2[N:69]=[C:68]([NH:70][C:71]3[CH:72]=[C:73]4[C:77](=[CH:78][CH:79]=3)[N:76]([C:80]([O:82][C:83]([CH3:86])([CH3:85])[CH3:84])=[O:81])[N:75]=[CH:74]4)[C:67]3[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=3)[N:61]=2)[CH:57]=[CH:58][CH:59]=1)=[O:10]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 162119581-Methyl-L-proline--water (1/1)HCID 66825994tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 59361945tert-butyl 5-(2-(3-((S)-1-methylpyrrolidine-2-carboxamido)phenyl)-quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A suspension of (S)-1-methylpyrrolidine-2-carboxylic acid monohydrate (14 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 oil product tert-butyl 5-(2-(3-((S)-1-methylpyrrolidine-2-carboxamido)phenyl)-quinazolin-4-ylamino)-1H-indazole-1-carboxylate.

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-3ebde1d2a1bf49e3883890c247c90f40
Source dataset
uspto-grants-2013_01
Patent number
US08357693B2

Reaction notes

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