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

Reaction equation

HRID 40350 reaction equation
[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

Participants

8

Reactant 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

Product 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)quinolineYield 33%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-efd9c9c05aee4096890d3aebeb33fd9c
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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