Triphenylphosphine → 6-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-3-(3-morpholinopropoxy)quinoline

HRID 40350

반응식

HRID 40350 반응식
[F:1][C:2]([F:30])([C:14]1[N:18]2[CH:19]=[C:20]([C:24]3[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=3)[CH:21]=[C:22]([F:23])[C:17]2=[N:16][N:15]=1)[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([OH:13])=[CH:6]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:51][CH2:52][CH2:53][N:54]1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>CO.C(Cl)Cl.C1COCC1>[F:30][C:2]([F:1])([C:14]1[N:18]2[CH:19]=[C:20]([C:24]3[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=3)[CH:21]=[C:22]([F:23])[C:17]2=[N:16][N:15]=1)[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([O:13][CH2:51][CH2:52][CH2:53][N:54]1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1)=[CH:6]2

참가 물질

8

반응물 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 1995763-Morpholino-1-propanolHCID 576910196-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)quinolin-3-ol

생성물 1

HCID 441811506-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-3-(3-morpholinopropoxy)quinoline수율 33%

시약·촉매·용매 3

HCID 887Methanol용매2회HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

To a flask charged with 6-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)quinolin-3-ol (17.3 mg, 42 μmol), was added triphenylphosphine (55 mg, 211 μmol), THF (1 mL), and 4-(3-hydroxypropyl)-morpholine, 95% (31 μl, 211 μmol). The mixture was placed under N2 and cooled to 0° C. Di-tert-butyl azodicarboxylate (49 mg, 211 μmol) was added as a solid in a single portion and the solution was allowed to warm to rt and was maintained for 48 h. The solution was concentrated for purification by MPLC (Teledine Isco combiFlash Companion). The crude residue was taken up in minimal CH2Cl2 and absorbed onto a 5 g loading cartridge and passed through a Redi-Sep® pre-packed silica gel column (40 g) using 99:1 CH2Cl2: MeOH to 90:10 CH2Cl2: MeOH gradient to afford 6-(difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)-3-(3-morpholinopropoxy)quinoline (7.5 mg, 33% yield) as a colorless solid. LRMS (ESI) m/z calcd for C27H27F3N7O2 (M+H) 538.2. found 538.2.

후처리

  1. temperatureto warm to rt
  2. temperaturewas maintained for 48 h
  3. concentrationThe solution was concentrated for purification by MPLC (Teledine Isco combiFlash Companion)
  4. customabsorbed onto a 5 g loading cartridge

출처 및 근거

ORD 기록
ord-efd9c9c05aee4096890d3aebeb33fd9c
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524900B2

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