1-Bromo-2-Chloroethane → tert-butyl 5-(6-(2-chloroethoxy)-2-[(3-phenyl)phenyl)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate

HRID 61620Notes

Reaction equation

HRID 61620 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:13]3[N:22]=[C:21]([NH:23][C:24]4[CH:25]=[C:26]5[C:30](=[CH:31][CH:32]=4)[N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[N:28]=[CH:27]5)[C:20]4[C:15](=[CH:16][C:17]([O:41][CH3:42])=[C:18]([OH:40])[CH:19]=4)[N:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:44][CH2:45][Cl:46].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:46][CH2:45][CH2:44][O:40][C:18]1[CH:19]=[C:20]2[C:15](=[CH:16][C:17]=1[O:41][CH3:42])[N:14]=[C:13]([C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:8]=1)[N:22]=[C:21]2[NH:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([C:33]([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:34])[N:28]=[CH:27]2

Participants

5

Reactant 3

HCID 78491-Bromo-2-ChloroethaneHCID 11430Potassium CarbonateHCID 59361909tert-butyl 5-(2-[(3-phenyl)phenyl]-6-hydroxy-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 59361996tert-butyl 5-(6-(2-chloroethoxy)-2-[(3-phenyl)phenyl)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylateYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of tert-butyl 5-(2-[(3-phenyl)phenyl]-6-hydroxy-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate (1.5 g, 2.68 mmole), 1-bromo-2-chloroethane (1.32 g, 0.76 mL, 9.17 mmole), K2CO3 (1.55 g, 11.21 mmole), and DMF (15 mL) was stirred at 85° C. for 2.5 h. The mixture was poured onto ice-water and the crude product was filtered. The product was then dissolved in a mixture of CH2Cl2 and CH3OH and the solution was concentrated in vacuo to give tert-butyl 5-(6-(2-chloroethoxy)-2-[(3-phenyl)phenyl)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate (1.55 g, 2.49 mmol, 93%). HPLC retention time 8.22 mins.

Workup

  1. additionThe mixture was poured onto ice-water
  2. filtrationthe crude product was filtered
  3. dissolutionThe product was then dissolved in a mixture of CH2Cl2 and CH3OH
  4. concentrationthe solution was concentrated in vacuo

Sources & evidence

ORD record
ord-490cc3debaa84910bcbd181462463361
Source dataset
uspto-grants-2016_09
Patent number
US09440961B2

Reaction notes

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