Potassium Carbonate → 4-{2-[(4-Bromophenyl)amino]quinazolin-6-yloxy}-(2-pyridyl)-n-methylcarboxamide

HRID 639357Notes

Reaction equation

HRID 639357 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14]([OH:19])[CH:15]=3)[N:10]=2)=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Cl[C:31]1[CH:36]=[CH:35][N:34]=[C:33]([C:37]([NH:39][CH3:40])=[O:38])[CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[N:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:19][C:31]4[CH:36]=[CH:35][N:34]=[C:33]([C:37]([NH:39][CH3:40])=[O:38])[CH:32]=4)[CH:15]=3)[N:10]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14768144-Chloro-N-methylpicolinamideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 592548812-[(4-Bromophenyl)amino]quinazolin-6-ol

Product 1

HCID 112362754-{2-[(4-Bromophenyl)amino]quinazolin-6-yloxy}-(2-pyridyl)-n-methylcarboxamideYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The mixture containing 2-[(4-bromophenyl)amino]quinazolin-6-ol (1 eq), potassiumbis(trimethylsilyl)amide (4eq) was stirred in dimethylformamide for 10 min at room temperature. To this mixture was added (4-chloro(2-pyridyl)-N-methylcarboxamide (1 eq) and Potassium carbonate (1.2 eq) and microwaved for 6 mins at 170° C. The reaction mixture was then concentrated and partitioned between ethyl acetate and water. The organic layer was separated and washed with brine, dried, filtered and concentrated. Purification on preparative chromatography yielded 4-{2-[(4-bromophenyl)amino]quinazolin-6-yloxy}-(2-pyridyl)-N-methylcarboxamide in 70-75% yield.

Workup

  1. custommicrowaved for 6 mins at 170° C
  2. concentrationThe reaction mixture was then concentrated
  3. custompartitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification on preparative chromatography

Sources & evidence

ORD record
ord-f4a94ad4ed6343c7bec9a9ed511181b6
Source dataset
uspto-grants-2010_04
Patent number
US07691866B2

Reaction notes

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