7-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)6-methoxyquinazoline → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-methyl-4H-1,2,4-triazol-3-ylthio)ethoxy)-quinazoline hydrochloride

HRID 1420978노트

반응식

HRID 1420978 반응식
Br[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[F:23])=[N:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:24][CH3:25].[CH3:26][N:27]1[CH:31]=[N:30][N:29]=[C:28]1[SH:32].CC(C)([O-])C.[K+]>CN(C=O)C>[ClH:22].[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][C:9]2[C:8]3[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][S:32][C:28]4[N:27]([CH3:26])[CH:31]=[N:30][N:29]=4)=[C:6]([O:24][CH3:25])[CH:7]=3)[N:12]=[CH:11][N:10]=2)=[C:17]([F:23])[CH:18]=1

참가 물질

5

반응물 3

HCID 187534227-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)6-methoxyquinazolineHCID 23665647Potassium tert-butoxideHCID 178481306HCID 178481306, 화합물

생성물 1

HCID 226249754-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-methyl-4H-1,2,4-triazol-3-ylthio)ethoxy)-quinazoline hydrochloride수율 157.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
40 °C

실험 절차

7-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (98 mg, 0.23 mmol) was added to a solution of 4-methyl-4H-1,2,4-triazole-3-thiol (40 mg, 0.34 mmol) and potassium-t-butoxide (36 mg, 0.32 mmol) in DMF (1 ml) and the mixture heated at 40° C. for 30 minutes. The reaction mixture was allowed to cool and was partitioned between ammonium chloride and ethyl acetate. The organic layer was separated, washed with water and brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with a gradient of methylene chloride/methanol (95/50 to 80/20). The purified solid product was triturated with ether and collected by filtration. The solid was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation and the residue was crystallised from methylene chloride and ether. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-methyl-4H-1,2,4-triazol-3-ylthio)ethoxy)-quinazoline hydrochloride (90 mg, 79%).

후처리

  1. temperatureto cool
  2. customwas partitioned between ammonium chloride and ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with a gradient of methylene chloride/methanol (95/50 to 80/20)
  9. customThe purified solid product was triturated with ether
  10. filtrationcollected by filtration
  11. dissolutionThe solid was dissolved in methylene chloride/methanol
  12. addition3M ethereal hydrogen chloride (0.5 ml) was added
  13. customThe volatiles were removed by evaporation
  14. customthe residue was crystallised from methylene chloride and ether
  15. filtrationThe solid was collected by filtration
  16. washwashed with ether
  17. customdried under vacuum

출처 및 근거

ORD 기록
ord-86ac8515d5ba42118292fbdc07eaa07d
출처 데이터셋
uspto-grants-2000_06
특허 번호
US06071921

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