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Pyridine → 1-(4-(2-(6-(1,3-Dioxan-2-yl)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-3-cyclopropylurea

HRID 1400899
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HRID 1400899 반응식
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[N:12]=[CH:11][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[CH:9][CH:8]=1.[N:31]1[CH:36]=C[CH:34]=[CH:33][CH:32]=1.ClC(OC1C=CC=CC=1)=[O:39].C1(N)CC1>CN(C=O)C.O>[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[N:12]=[CH:11][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:22][C:23]3[CH:29]=[CH:28][C:26]([NH:27][C:36]([NH:31][CH:32]4[CH2:34][CH2:33]4)=[O:39])=[CH:25][C:24]=3[F:30])[CH:14]=2)=[CH:9][CH:8]=1
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참가 물질

7

반응물 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 584748694-(2-(6-(1,3-Dioxan-2-yl)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluoroaniline

생성물 1

HCID 674423941-(4-(2-(6-(1,3-Dioxan-2-yl)pyridin-3-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-3-cyclopropylurea수율 36%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

To a stirred solution of compound 280 (6.32 g, 14.92 mmol) and pyridine (2.41 mL, 17.91 mmol) in DMF (70 mL) at 0° C. was added phenyl chloroformate (2.25 mL, 17.91 mmol). After 30 min cyclopropylamine (2.63 mL, 37.3 mmol) was added at RT and the reaction mixture was heated at 60° C. for 45 min. After cooling to RT the reaction mixture was diluted with water to form a precipitate that was collected by filtration, dried and purified by Biotage (SNAP 100 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 10/90 over 20 CV), to produce a material that upon trituration with EtOAc afforded the title compound 281 (2.71 g, 5.35 mmol, 36% yield) as a beige solid. MS (m/z): 507.2 (M+H).

후처리

  1. temperatureAfter cooling to RT the reaction mixture
  2. customto form a precipitate that
  3. filtrationwas collected by filtration
  4. customdried
  5. custompurified by Biotage (SNAP 100 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 0/100 to 10/90 over 20 CV)
  6. customto produce a material that upon trituration with EtOAc

출처 및 근거

ORD 기록
ord-76f579626abb467fabaa949f7d9f7e9e
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08906852B2

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