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Tributylphosphine → 4-(4-Chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline

HRID 453995
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HRID 453995 반응식
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.C(P(CCCC)CCCC)CCC.[O:36]=[S:37]1(=[O:47])[CH2:42][CH2:41][N:40]([CH2:43][CH2:44][CH2:45]O)[CH2:39][CH2:38]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>ClCCl.CCOCC>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:45][CH2:44][CH2:43][N:40]4[CH2:39][CH2:38][S:37](=[O:47])(=[O:36])[CH2:42][CH2:41]4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 114354734-(3-Hydroxypropyl)thiomorpholine 1,1-DioxideHCID 1356162044-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline

생성물 1

HCID 219359994-(4-Chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline수율 70%

시약·촉매·용매

2
HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매

실험 절차

4-(4-Chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (5.0 g, 15.6 mmol) was suspended in dichloromethane (150 ml) and tributylphosphine (11.1 ml, 44.6 mmol) was added followed by stirring at ambient temperature for 30 minutes. To this mixture was added 3-(1,1-dioxothiomorpholino)-1-propanol (4.2 g, 21.8 mmol) followed by the addition of 1,1′-(azodicarbonyl)dipiperidine (11.7 g, 46.4 mmol) in portions. The mixture was stirred at ambient temperature overnight then diluted with ether (300 ml) and the precipitate was removed by filtration. The residue was chromatographed on silica eluting with dichloromethane and methanol (95/5). The relevant fractions were combined and evaporated to give a solid which was triturated with ethyl acetate filtered and dried to give 4-(4-chloro-2-fluorophenoxy)-7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxyquinazoline (5.4 g, 70%).

후처리

  1. stirringThe mixture was stirred at ambient temperature overnight
  2. customthe precipitate was removed by filtration
  3. customThe residue was chromatographed on silica eluting with dichloromethane and methanol (95/5)
  4. customevaporated
  5. customto give a solid which
  6. customwas triturated with ethyl acetate
  7. filtrationfiltered
  8. customdried

출처 및 근거

ORD 기록
ord-177561d139434939a020630c8378a071
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08492560B2

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