Hydrochloric Acid → 4-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-(4-pyridyl)propoxy)quinazoline hydrochloride

HRID 1384568노트

반응식

HRID 1384568 반응식
[OH-].[Na+].[Cl:3][C:4]1[C:32]([O:33]C(OC)=O)=[CH:31][C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:6]([F:38])[CH:5]=1.O.Cl>CO>[ClH:3].[Cl:3][C:4]1[C:32]([OH:33])=[CH:31][C:7]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH2:22][CH2:23][CH2:24][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)=[C:16]([O:19][CH3:20])[CH:17]=3)[N:12]=[CH:11][N:10]=2)=[C:6]([F:38])[CH:5]=1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 22624977HCID 22624977, 화합물

생성물 1

HCID 226248824-(4-Chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-(4-pyridyl)propoxy)quinazoline hydrochloride수율 150.4%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

2M Aqueous sodium hydroxide (1.5 ml mmol) was added to a solution of 4-(4-chloro-2-fluoro-5-methoxycarbonyloxyanilino)-6-methoxy-7-(3-(4-pyridyl)propoxy)quinazoline (1.28 g, 2.5 mmol) in methanol (13 ml) and the mixture stirred for 2 hours at ambient temperature. Water was added and the mixture was adjusted to pH7 with 2M hydrochloric acid. The resulting precipitate was collected by filtration, washed with water and dried under vacuum. This solid was dissolved in methylene chloride (30 ml) and methanol (5 ml) and a solution of 5M hydrogen chloride in isopropanol (2.5 ml) was added. The solution was diluted with isopropanol and concentrated under vacuum to a total volume of 10 ml. The resulting solid was collected by filtration, washed with isopropanol and then ether and dried under vacuum to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-(4-pyridyl)propoxy)quinazoline hydrochloride (924 mg, 70%). 1H NMR Spectrum: (DMSOd6) 2.3(t, 2H); 3.12(t, 2H); 4.0(s, 3H); 4.28(t, 2H); 7.18(d, 1H); 7.4(s, 1H); 7.52(d, 1H); 7.95(d, 2H); 8.32(s, 1H); 8.82(s, 1H); 8.84(d, 2H); 10.65(s, 1H); 11.65(br s, 1H) MS-ESI: 455 [MH]+

후처리

  1. filtrationThe resulting precipitate was collected by filtration
  2. washwashed with water
  3. customdried under vacuum
  4. dissolutionThis solid was dissolved in methylene chloride (30 ml)
  5. additionmethanol (5 ml) and a solution of 5M hydrogen chloride in isopropanol (2.5 ml) was added
  6. additionThe solution was diluted with isopropanol
  7. concentrationconcentrated under vacuum to a total volume of 10 ml
  8. filtrationThe resulting solid was collected by filtration
  9. washwashed with isopropanol
  10. dry with materialether and dried under vacuum

출처 및 근거

ORD 기록
ord-3d7463f08d37486aa1868cbac8194311
출처 데이터셋
uspto-grants-2001_07
특허 번호
US06258951B1

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