Diisopropylethylamine → 4-[6-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-3-phenyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 2279088Notes

Reaction equation

HRID 2279088 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]([C:31]([OH:33])=O)[C:18]3[C:23]([CH3:24])=[N:22][N:21]([CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[C:19]=3[N:20]=2)=[C:11]([F:34])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[C:44]([O:48][C:49]([N:51]1[CH2:56][CH2:55][NH:54][CH:53]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[CH2:52]1)=[O:50])([CH3:47])([CH3:46])[CH3:45]>C(Cl)Cl.O>[C:44]([O:48][C:49]([N:51]1[CH2:56][CH2:55][N:54]([C:31]([C:17]2[C:18]3[C:23]([CH3:24])=[N:22][N:21]([CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[C:19]=3[N:20]=[C:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[CH:10][C:11]=3[F:34])[CH:16]=2)=[O:33])[CH:53]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[CH2:52]1)=[O:50])([CH3:47])([CH3:45])[CH3:46]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 2735358Tert-butyl 3-phenylpiperazine-1-carboxylateHCID 866803216-(4-benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

Product 1

HCID 900135244-[6-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-3-phenyl-piperazine-1-carboxylic acid tert-butyl esterYield 103.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 571 mg of 6-(4-benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid in 14 ml of DCM were added 0.64 ml of Hünig's base, 408 mg of BEP and 390 mg of 3-phenyl-piperazine-1-carboxylic acid tert-butyl ester. The reaction was stirred overnight at r.t. For workup it was diluted with water and DCM and the layers were separated. The organic layer was washed with water twice, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica, heptane/EtOAc gradient) to obtain 900 mg (100%) of the title compound.

Workup

  1. customthe layers were separated
  2. washThe organic layer was washed with water twice
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (silica, heptane/EtOAc gradient)

Sources & evidence

ORD record
ord-a0061fb4e77d4edf875688ee3c2c9410
Source dataset
uspto-grants-2015_09
Patent number
US09133181B2

Reaction notes

Loading…