Tributylphosphine → 4-(4-Chloro-2-fluoroanilino)-7-(2-ethoxycarbonylpyrid-4-yl)methoxy-6-methoxyquinazoline

HRID 1737631노트

반응식

HRID 1737631 반응식
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:19][C:20]1[CH:39]=[CH:38][C:23]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([OH:37])=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:22]([F:40])[CH:21]=1.O[CH2:42][C:43]1[CH:48]=[CH:47][N:46]=[C:45]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH:44]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl>[Cl:19][C:20]1[CH:39]=[CH:38][C:23]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([O:37][CH2:42][C:43]4[CH:48]=[CH:47][N:46]=[C:45]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH:44]=4)=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:22]([F:40])[CH:21]=1

참가 물질

6

반응물 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 14541449Ethyl 4-(hydroxymethyl)picolinateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

생성물 1

HCID 226249784-(4-Chloro-2-fluoroanilino)-7-(2-ethoxycarbonylpyrid-4-yl)methoxy-6-methoxyquinazoline수율 60%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

1,1'-(azodicarbonyl)dipiperidine (840 mg, 3 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (315 mg, 1 mmol), ethyl 4-hydroxymethyl-2-pyridinecarboxylate (250 mg, 1.4 mmol), (J. Het. Chem. 1993, 30, 631-635) and tributylphosphine (800 μl, 3 mmol) in methylene chloride (50 ml) at 0° C. The mixture was allowed to warm to ambient temperature over 2 hours, the insolubles were removed by filtration and the filtrate was washed with water and brine, dried (Na2SO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (10:0 increasing to 9:1). The purified product was recrystallised from methylene chloride/hexane to give 4-(4-chloro-2-fluoroanilino)-7-(2-ethoxycarbonylpyrid-4-yl)methoxy-6-methoxyquinazoline (285 mg, 60%). m.p. 212-214° C.

후처리

  1. customthe insolubles were removed by filtration
  2. washthe filtrate was washed with water and brine
  3. dry with materialdried (Na2SO4)
  4. customthe solvent removed by evaporation
  5. customThe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol (10:0 increasing to 9:1)
  7. customThe purified product was recrystallised from methylene chloride/hexane

출처 및 근거

ORD 기록
ord-ae5a3cd8b0c947be8ecc9341e9d5e1e1
출처 데이터셋
uspto-grants-1999_10
특허 번호
US05962458

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