Triethylamine → 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochloride

HRID 1384604노트

반응식

HRID 1384604 반응식
[C:1]([Cl:9])(=[O:8])[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.O.Cl.[Cl:12][C:13]1[CH:36]=[CH:35][C:16]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][NH:33][CH3:34])=[C:25]([O:28][CH3:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)=[C:15]([F:37])[CH:14]=1.C(N(CC)CC)C>C(Cl)Cl>[ClH:9].[Cl:12][C:13]1[CH:36]=[CH:35][C:16]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][N:33]([CH3:34])[C:1]([C:2]4[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=4)=[O:8])=[C:25]([O:28][CH3:29])[CH:26]=3)[N:21]=[CH:20][N:19]=2)=[C:15]([F:37])[CH:14]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 417436Pyridine-4-carbonyl chlorideHCID 226249694-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(methylamino)ethoxy)quinazoline hydrochloride hydrate

생성물 1

HCID 226250114-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochloride수율 144.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Isonicotinoyl chloride (36 mg, 0.2 mmol) was added to a suspension of 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(methylamino)ethoxy)quinazoline hydrochloride hydrate (90 mg, 0.1 mmol), (prepared as described for the starting material in Example 54), in methylene chloride (3 ml) and triethylamine (80 mg, 0.8 mmol) was then added dropwise. The mixture was stirred for 30 minutes at ambient temperature and the solvent was then removed by evaporation. The residue was partitioned between ethyl acetate and water, the organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml) was added. The suspension was diluted with ether, the precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochloride (75 mg, 67%). 1H NMR Spectrum: (DMSOd6; CF3COOD; 95° C.) 3.1(s, 3H); 3.8-3.9(br s, 2H); 4.1(s, 3H); 4.4-4.6(br s, 2H); 7.4-7.45(m, 2H); 7.55(dd, 1H); 7.65(t, 1H); 7.9-8.0(br s, 2H); 8.28(s, 1H); 8.8(s, 1H); 8.95(s, 2H) MS-ESI: 482 [MH]+

후처리

  1. custom(prepared
  2. customthe solvent was then removed by evaporation
  3. customThe residue was partitioned between ethyl acetate and water
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. dissolutionThe residue was dissolved in methylene chloride/methanol
  9. addition3M ethereal hydrogen chloride (0.5 ml) was added
  10. additionThe suspension was diluted with ether
  11. filtrationthe precipitate was collected by filtration
  12. washwashed with ether
  13. customdried under vacuum

출처 및 근거

ORD 기록
ord-fae3cf49a70148a2ac1e12ca45d77d3d
출처 데이터셋
uspto-grants-2001_07
특허 번호
US06258951B1

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