tert-butyl 5-(2-(3-(2-(isopropylamino)-2-oxoethoxy)phenyl)-7-methoxy-6-(2-methoxyethoxy)quinazolin-4-ylamino)-1H-indazole-1-carboxylate → 2-(3-(4-(1H-indazol-5-ylamino)-7-methoxy-6-(2-methoxyethoxy)-quinazolin-2-yl)phenoxy)-N-isopropylacetamide

HRID 1808536Notes

Reaction equation

HRID 1808536 reaction equation
[CH:1]([NH:4][C:5](=[O:48])[CH2:6][O:7][C:8]1[CH:9]=[C:10]([C:14]2[N:23]=[C:22]([NH:24][C:25]3[CH:26]=[C:27]4[C:31](=[CH:32][CH:33]=3)[N:30](C(OC(C)(C)C)=O)[N:29]=[CH:28]4)[C:21]3[C:16](=[CH:17][C:18]([O:46][CH3:47])=[C:19]([O:41][CH2:42][CH2:43][O:44][CH3:45])[CH:20]=3)[N:15]=2)[CH:11]=[CH:12][CH:13]=1)([CH3:3])[CH3:2]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[NH:30]1[C:31]2[C:27](=[CH:26][C:25]([NH:24][C:22]3[C:21]4[C:16](=[CH:17][C:18]([O:46][CH3:47])=[C:19]([O:41][CH2:42][CH2:43][O:44][CH3:45])[CH:20]=4)[N:15]=[C:14]([C:10]4[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=4)[O:7][CH2:6][C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[O:48])[N:23]=3)=[CH:33][CH:32]=2)[CH:28]=[N:29]1

Participants

4

Reactant 1

HCID 59361834tert-butyl 5-(2-(3-(2-(isopropylamino)-2-oxoethoxy)phenyl)-7-methoxy-6-(2-methoxyethoxy)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 250120872-(3-(4-(1H-indazol-5-ylamino)-7-methoxy-6-(2-methoxyethoxy)-quinazolin-2-yl)phenoxy)-N-isopropylacetamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

The crude tert-butyl 5-(2-(3-(2-(isopropylamino)-2-oxoethoxy)phenyl)-7-methoxy-6-(2-methoxyethoxy)quinazolin-4-ylamino)-1H-indazole-1-carboxylate from the previous step was taken up in CH2Cl2 (2 mL) and TFA (5 mL). The mixture was stirred at RT for 2 h. The mixture was concentrated in vacuo and a portion of the residue was purified by preparative HPLC (10-35-90, 10-30-90, 0-15-90, 5-20-90 and 20-40-90 methods) to give 2-(3-(4-(1H-indazol-5-ylamino)-7-methoxy-6-(2-methoxyethoxy)-quinazolin-2-yl)phenoxy)-N-isopropylacetamide (0.039 g, 68.4 μmol). MS 557 (M+1). HPLC retention time 5.48 mins.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customa portion of the residue was purified by preparative HPLC (10-35-90, 10-30-90, 0-15-90, 5-20-90 and 20-40-90 methods)

Sources & evidence

ORD record
ord-4252f261e6534f0694d23f5e0092dc84
Source dataset
uspto-grants-2013_01
Patent number
US08357693B2

Reaction notes

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