Ethyl trifluoroacetate → 2,2,2-trifluoro-N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-methylsulfanylphenyl)propan-2-yl]acetamide

HRID 13017

반응식

HRID 13017 반응식
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[CH:13][C:14]([O:18][C@H:19]([C:23]4[CH:28]=[CH:27][C:26]([S:29][CH3:30])=[CH:25][CH:24]=4)[C@@H:20]([NH2:22])[CH3:21])=[CH:15][CH:16]=3)[CH:11]=[N:10]2)=[CH:5][CH:4]=1.CN(C)C(N(C)C)=N.[F:39][C:40]([F:47])([F:46])[C:41](OCC)=[O:42]>CO>[F:39][C:40]([F:47])([F:46])[C:41]([NH:22][C@@H:20]([CH3:21])[C@H:19]([O:18][C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][CH:15]=1)[N:9]([C:6]1[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=1)[N:10]=[CH:11]2)[C:23]1[CH:24]=[CH:25][C:26]([S:29][CH3:30])=[CH:27][CH:28]=1)=[O:42]

참가 물질

5

반응물 3

HCID 9794Ethyl trifluoroacetateHCID 664601,1,3,3-TetramethylguanidineHCID 66687724(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine hydrochloride

생성물 1

HCID 250136542,2,2-trifluoro-N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-methylsulfanylphenyl)propan-2-yl]acetamide

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

(1R,2S)-1-{[1-(4-Fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine hydrochloride (9a) (150 mg, 0.34 mmol) was dissolved in MeOH (2 mL). 1,1,3,3-tetramethylguanidine (128 μL, 1.02 mmol) was added and the mixture was stirred for 5 min, ethyl trifluoroacetate (83 μL, 0.7 mmol) was added and the reaction mixture was stirred at r.t. for 2.5 h. The reaction mixture was evaporated and the residual material was purified by semi-preparative HPLC using a Kromasil® C18 250×20 mm, 5 μm column. Flow 10 mL/min, 20 min gradient of 20%-90% MeCN in water followed by isocratic final concentration until product had eluted. UV=254 nm was used for detection. Fractions with product was combined and lyophilized to afford the title compound as a colourless solid. Yield 128 mg (74%)

후처리

  1. stirringthe reaction mixture was stirred at r.t. for 2.5 h
  2. customThe reaction mixture was evaporated
  3. customthe residual material was purified by semi-preparative HPLC
  4. customFlow 10 mL/min, 20 min gradient of 20%-90% MeCN in water
  5. concentrationconcentration until product
  6. washhad eluted

출처 및 근거

ORD 기록
ord-c85fda72d8cd4530a5948340759c9843
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728030B2

연결된 노트

불러오는 중…