Diisopropylethylamine → 4-[6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2,2-diethyl-5,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 2279122Notes

Reaction equation

HRID 2279122 reaction equation
[Br:1][C:2]1[N:7]=[C:6]2[N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:9]=[C:10]([CH3:11])[C:5]2=[C:4]([CH2:18]OS(C)(=O)=O)[CH:3]=1.[C:24]([O:28][C:29]([N:31]1[CH2:36][C:35]([CH3:38])([CH3:37])[NH:34][CH2:33][C:32]1([CH2:41][CH3:42])[CH2:39][CH3:40])=[O:30])([CH3:27])([CH3:26])[CH3:25].CCN(C(C)C)C(C)C>C1COCC1.O>[C:24]([O:28][C:29]([N:31]1[CH2:36][C:35]([CH3:38])([CH3:37])[N:34]([CH2:18][C:4]2[CH:3]=[C:2]([Br:1])[N:7]=[C:6]3[N:8]([CH:12]4[CH2:17][CH2:16][CH2:15][CH2:14][O:13]4)[N:9]=[C:10]([CH3:11])[C:5]=23)[CH2:33][C:32]1([CH2:41][CH3:42])[CH2:39][CH3:40])=[O:30])([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 90013581Methanesulfonic acid 6-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl esterHCID 900138422,2-Diethyl-5,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 900140904-[6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-2,2-diethyl-5,5-dimethyl-piperazine-1-carboxylic acid tert-butyl esterYield 51.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 500 mg of methanesulfonic acid 6-bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl ester, 400 mg of 2,2-diethyl-5,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester and 0.43 ml of DIPEA in 8 ml of dry THF was heated to 160° C. for 30 min in a microwave reactor. For workup the mixture was taken up in water and ethyl acetate, the phases were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulphate, filtrated and concentrated in vacuo and the resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate). 369 mg (50%) of the title compound were obtained.

Workup

  1. customethyl acetate, the phases were separated
  2. extractionthe aqueous phase was extracted with ethyl acetate
  3. dry with materialThe combined organic phases were dried over sodium sulphate
  4. filtrationfiltrated
  5. concentrationconcentrated in vacuo
  6. customthe resulting residue was purified by flash chromatography (silica, heptane/ethyl acetate)

Sources & evidence

ORD record
ord-6469b407ddd34e8e9df8f259dd0fb3c2
Source dataset
uspto-grants-2015_09
Patent number
US09133181B2

Reaction notes

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