3-Morpholino-1-propanol → 4-[(3,4-Dichloro-6-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline

HRID 346417

반응식

HRID 346417 반응식
[Na].[N:2]1([CH2:8][CH2:9][CH2:10][OH:11])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[Cl:12][C:13]1[CH:14]=[C:15]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[C:16]([F:20])=[CH:17][C:18]=1[Cl:19]>C1COCC1>[Cl:12][C:13]1[CH:14]=[C:15]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:11][CH2:10][CH2:9][CH2:8][N:2]4[CH2:7][CH2:6][O:5][CH2:4][CH2:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[C:16]([F:20])=[CH:17][C:18]=1[Cl:19]

참가 물질

5

반응물 3

HCID 1995763-Morpholino-1-propanolHCID 5360545SodiumHCID 111761854-[(3,4-Dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline

생성물 1

HCID 210800014-[(3,4-Dichloro-6-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline수율 72%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
20 °C

실험 절차

Sodium metal (5 equivalents) was added, under nitrogen atmosphere, to a solution of 3-(4-morpholinyl)-1-propanol (4 equivalents) in THF. The obtained suspension was stirred at 20° C. for two hours and was thereafter cannulated, under nitrogen atmosphere, into a solution of 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline. The reaction mixture was refluxed for 18 hours, the solvent was thereafter partially removed under reduced pressure and the residue was diluted with water and extracted with ethyl acetate. Drying the combined organic extracts, evaporation and silica gel chromatography (using a mixture of 20% MeOH/30% CH2Cl2/50% EtOAc as elute) gave 4-[(3,4-dichloro-6-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-nitroquinazoline in 72% yield.

후처리

  1. temperatureThe reaction mixture was refluxed for 18 hours
  2. customthe solvent was thereafter partially removed under reduced pressure
  3. additionthe residue was diluted with water
  4. extractionextracted with ethyl acetate
  5. customDrying
  6. customthe combined organic extracts, evaporation and silica gel chromatography (
  7. additiona mixture of 20% MeOH/30% CH2Cl2/50% EtOAc
  8. washas elute)

출처 및 근거

ORD 기록
ord-44f5507bc07f4cd99812ba644cbcabc3
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07172749B2

연결된 노트

불러오는 중…