Potassium Carbonate → 1,1-Dimethylethyl 4-[5-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate

HRID 2199688Notes

Reaction equation

HRID 2199688 reaction equation
Cl[CH2:2][C:3]1[O:7][N:6]=[C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[N:4]=1.[Cl:21][C:22]1[CH:23]=[C:24]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([OH:42])=[C:37]([O:40][CH3:41])[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:25]=[CH:26][C:27]=1[Cl:28].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:21][C:22]1[CH:23]=[C:24]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([O:42][CH2:2][C:3]4[O:7][N:6]=[C:5]([N:8]5[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]5)[N:4]=4)=[C:37]([O:40][CH3:41])[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:25]=[CH:26][C:27]=1[Cl:28]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 666739121,1-Dimethylethyl 4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylateHCID 1362726214-(3,4-Dichloroanilino)-6-methoxyquinazolin-7(1H)-one

Product 1

HCID 578027141,1-Dimethylethyl 4-[5-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylateYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

1,1-dimethylethyl 4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate (173.6 mg, 0.57 mmol), 4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-ol (154 mg, 0.46 mmol) and potassium carbonate (315 mg, 2.85 mmol) were taken into DMF (2 mL) and the mixture was heated to 50° C. for one hour. The mixture was then cooled to room temperature and partitioned with ethyl acetate and water. The organic layer was washed once more with water and the organic layer was partitioned again with water. A precipitate forms in the organic layer at this point and hexanes was added to the biphasic mixture in portions until formation of the precipitate is complete. The solid product was then collected by filtration. The solid residue was suspended in hot methanol and diluted with water followed by collection of the solid by filtration. The solid was washed with ethyl ether and dried in vacuo to give 1,1-dimethylethyl 4-[5-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate (170.7 mg, 62% yield) as a tan solid. 1H-NMR (400 MHz, DMSO-d6): 9.65 (s, 1H), 8.54 (s, 1H), 8.23 (d, 1H), 7.88-7.86 (m, 2H), 7.63 (d, 1H), 7.32 (s, 1H), 5.58 (s, 2H), 3.98 (s, 3H), 3.43-3.40 (m, 4H), 3.34-3.32 (m, 4H), 1.41 (s, 9H); MS (EI) for C27H29Cl2N7O5: 602 (MH+).

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. custompartitioned with ethyl acetate and water
  3. washThe organic layer was washed once more with water
  4. customthe organic layer was partitioned again with water
  5. additionA precipitate forms in the organic layer at this point and hexanes was added to the biphasic mixture in portions until formation of the precipitate
  6. filtrationThe solid product was then collected by filtration
  7. additiondiluted with water
  8. filtrationfollowed by collection of the solid by filtration
  9. washThe solid was washed with ethyl ether
  10. customdried in vacuo

Sources & evidence

ORD record
ord-3826c0b23cb1433d9b939095e7143711
Source dataset
uspto-grants-2016_06
Patent number
US09359332B2

Reaction notes

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