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Trifluoroacetic acid → 1-(3-cyano-phenyl)-3-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-urea

HRID 571814
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인쇄 미리보기

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HRID 571814 반응식
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][O:18][C@H:17]([C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([C:37]#[N:38])[CH:32]=3)=[O:29])=[C:23]([F:39])[CH:22]=2)[CH2:16]1)=O)(C)(C)C.[OH-].[Na+]>O.C(#N)C>[C:37]([C:33]1[CH:32]=[C:31]([NH:30][C:28]([NH:27][C:24]2[CH:25]=[CH:26][C:21]([C@H:17]3[O:18][CH2:19][CH2:20][NH:15][CH2:16]3)=[CH:22][C:23]=2[F:39])=[O:29])[CH:36]=[CH:35][CH:34]=1)#[N:38]
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참가 물질

6

반응물 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 71087021(R)-2-{4-[3-(3-cyano-phenyl)-ureido]-3-fluoro-phenyl}-morpholine-4-carboxylic acid tert-butyl ester

생성물 1

HCID 710869101-(3-cyano-phenyl)-3-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-urea수율 68.5%

시약·촉매·용매 2

HCID 962Water용매
HCID 6342
Acetonitrile
용매

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온도
80 °C

실험 절차

To a stirred solution of trifluoroacetic acid (216 μl) in water (4.5 ml) was added a solution of (R)-2-{4-[3-(3-cyano-phenyl)-ureido]-3-fluoro-phenyl}-morpholine-4-carboxylic acid tert-butyl ester (85 mg) in acetonitrile (2 ml). The reaction mixture was then capped and the mixture was shaken at 80° C. for 3 h. The reaction mixture was then cooled to room temperature and poured into 1 M aq. NaOH and the resulting mixture was extracted twice with EtOAc. The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis); gradient: heptane/EtOAc/MeOH) to afford 1-(3-cyano-phenyl)-3-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-urea (45 mg, 61%) as a white solid. MS (ISP): 341.1 ([M+H]+).

후처리

  1. customThe reaction mixture was then capped
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. extractionthe resulting mixture was extracted twice with EtOAc
  4. dry with materialThe organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash column chromatography (Isolute® Flash-NH2 from Separtis)

출처 및 근거

ORD 기록
ord-a6a670f42a574e0996588f5cf3d3d3e1
출처 데이터셋
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09029370B2

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