Diisopropylethylamine → 6-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (1-benzyl-4-phenyl-piperidin-4-yl)-amide

HRID 2360700Notes

Reaction equation

HRID 2360700 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]([C:31](O)=[O:32])[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.[CH3:35][CH2:36][N:37]([CH:41]([CH3:43])C)[CH:38]([CH3:40])C>ClC(Cl)C>[CH2:41]([N:37]1[CH2:36][CH2:35][C:15]([NH:20][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:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:10][C:11]=3[F:34])[CH:16]=2)=[O:32])([C:12]2[CH:13]=[CH:14][CH:9]=[CH:10][CH:11]=2)[CH2:40][CH2:38]1)[C:43]1[CH:4]=[CH:3][CH:2]=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 81531DiisopropylethylamineHCID 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 866803236-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (1-benzyl-4-phenyl-piperidin-4-yl)-amideYield 59%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of 6-(4-benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (304 mg), amine (200 (200 mg), DIPEA (340 μL) and BEP (190 mg) in dichloroethane (6.5 mL) was stirred at r.t. for 90 min. The solvent was distilled off in vacuo, the residue was re-dissolved in ethyl acetate (20 mL) and washed twice with water, twice with saturated sodium bicarbonate solution and with brine, then dried over magnesium sulfate. After evaporation of the solvents, the residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient) giving 278 mg (59%) of the title compound.

Workup

  1. distillationThe solvent was distilled off in vacuo
  2. dissolutionthe residue was re-dissolved in ethyl acetate (20 mL)
  3. washwashed twice with water, twice with saturated sodium bicarbonate solution and with brine
  4. dry with materialdried over magnesium sulfate
  5. customAfter evaporation of the solvents
  6. customthe residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-180696ac3cd045dd8264e3401e30896f
Source dataset
uspto-grants-2014_04
Patent number
US08686150B2

Reaction notes

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