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

HRID 2279159Notes

Reaction equation

HRID 2279159 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]([C:27](O)=[O:28])[C:14]3[C:19]([CH3:20])=[N:18][N:17]([CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][O:22]4)[C:15]=3[N:16]=2)=[CH:7][CH:6]=1.CCN(C(C)C)C(C)C.[C:39]([O:43][C:44]([N:46]1[CH2:51][CH2:50][NH:49][C@H:48]([CH2:52][C:53]([F:56])([F:55])[F:54])[CH2:47]1)=[O:45])([CH3:42])([CH3:41])[CH3:40]>C(Cl)Cl.O>[C:39]([O:43][C:44]([N:46]1[CH2:51][CH2:50][N:49]([C:27]([C:13]2[C:14]3[C:19]([CH3:20])=[N:18][N:17]([CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][O:22]4)[C:15]=3[N:16]=[C:11]([C:8]3[CH:9]=[CH:10][C:5]([O:4][CH2:3][O:2][CH3:1])=[CH:6][CH:7]=3)[CH:12]=2)=[O:28])[C@H:48]([CH2:52][C:53]([F:55])([F:56])[F:54])[CH2:47]1)=[O:45])([CH3:42])([CH3:40])[CH3:41]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 72210106(R)-3-(2,2,2-Trifluoro-ethyl)-piperazine-1-carboxylic acid tert-butyl esterHCID 900138076-(4-Methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

Product 1

HCID 90013556(R)-4-[6-(4-Methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-3-(2,2,2-trifluoro-ethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 0.80 g of 6-(4-methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid in 12 ml of DCM were added 1 ml of Hünig's base, 0.48 g of BEP and 0.50 g of (R)-3-(2,2,2-trifluoroethyl)-piperazine-1-carboxylic acid tert-butyl ester. The reaction was stirred at r.t. for 2 d. 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 0.58 g (60%) 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-88ee32782b944209b60c3720f6321a5d
Source dataset
uspto-grants-2015_09
Patent number
US09133181B2

Reaction notes

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