Dichloromethane → Tert-butyl 4-(2-(3-chloro-4-morpholinophenylamino)-5-methylquinazolin-8-yloxy)piperidine-1-carboxylate

HRID 2079677Notes

Reaction equation

HRID 2079677 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]([O:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)=[C:8]2[C:3]=1[CH:4]=[N:5][C:6]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[C:29]([Cl:39])[CH:28]=1)=[N:7]2.[C:40](=O)([O-])[O-].[Na+].[Na+].CB1OB(C)OB(C)O1.C(Cl)Cl>CN(C=O)C>[Cl:39][C:29]1[CH:28]=[C:27]([NH:26][C:6]2[N:5]=[CH:4][C:3]3[C:8](=[C:9]([O:12][CH:13]4[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18]4)[CH:10]=[CH:11][C:2]=3[CH3:40])[N:7]=2)[CH:32]=[CH:31][C:30]=1[N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 574072TrimethylboroxineHCID 59199220Tert-butyl 4-(5-bromo-2-(3-chloro-4-morpholinophenylamino) quinazolin-8-yloxy)piperidine-1-carboxylate

Product 1

HCID 67102195Tert-butyl 4-(2-(3-chloro-4-morpholinophenylamino)-5-methylquinazolin-8-yloxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 4-(5-bromo-2-(3-chloro-4-morpholinophenylamino) quinazolin-8-yloxy)piperidine-1-carboxylate (See example 45 for synthesis) (1 eq) in DMF was added 2M sodium carbonate solution, trimethylboroxine (3 eq) and Pd (dppf)2Cl2.CH2Cl2 (0.05 eq). The reaction mixture was micro waved for 10 min at 120° C. The reaction mixture was then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried, concentrated and purified by semi-preparative HPLC to provide pure product. ES/MS m/z 554.1 (MH+).

Workup

  1. customThe reaction mixture was then partitioned between ethyl acetate and water
  2. washThe organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated
  5. custompurified by semi-preparative HPLC
  6. customto provide pure product

Sources & evidence

ORD record
ord-c625f3e3964748a499dfb8e8b1bfa168
Source dataset
uspto-grants-2011_04
Patent number
US07932262B2

Reaction notes

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