Sodium Carbonate → Methyl 2-methyl-2-((2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)butanoate

HRID 1844384Notes

Reaction equation

HRID 1844384 reaction equation
[C:1]1([CH3:28])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.Cl[C:30]1[N:35]=[C:34]([NH:36][C:37]([CH3:44])([CH2:42][CH3:43])[C:38]([O:40][CH3:41])=[O:39])[CH:33]=[CH:32][N:31]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[CH3:44][C:37]([NH:36][C:34]1[CH:33]=[CH:32][N:31]=[C:30]([C:12]2[C:13]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[N:10]([S:7]([C:4]3[CH:5]=[CH:6][C:1]([CH3:28])=[CH:2][CH:3]=3)(=[O:9])=[O:8])[CH:11]=2)[N:35]=1)([CH2:42][CH3:43])[C:38]([O:40][CH3:41])=[O:39]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 497589593-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 86682097Methyl 2-((2-chloropyrimidin-4-yl)amino)-2-methylbutanoate

Product 1

HCID 71187500Methyl 2-methyl-2-((2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)butanoateYield 161.8%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A 500 mL pressure vessel was charged with 80 mL DME, 1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (4.4 g, 11.05 mmol), methyl 2-((2-chloropyrimidin-4-yl)amino)-2-methylbutanoate, (2.44 g, 10.05 mmol), sodium carbonate (10 mL of 2M aq solution, 20 mmol) and degassed the mixture with a nitrogen stream for 30 min. Then, Pd(dppf)Cl2 was added, the flask sealed and heated to 90° C. for 15 hours. The mixture was cooled and filtered through Florisil. Evaporation under vacuum gave 7.8 g of a brown residue which was purified by flash chromatography, (0-80% ethyl acetate-hexane affording 3.9 g (81%) methyl 2-methyl-2-((2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)butanoate. 1H NMR (CDCl3) 8.83 (dd, 1H), 8.52 (s, 1H), 8.44 (dd, 1H), 7.28 (dd, 4H), 6.27 (d, 1H), 5.29 (s, 1H), 3.74 (d, 3H), 2.38 (s, 3H), 2.34-2.15 (m, 1H), 2.18-2.00 (m, 2H), 1.98 (s, 2H), 1.74 (s, 3H), 1.34-1.17 (m, 15H), 1.03 (m, 3H). m/e m+1 480.25

Workup

  1. customdegassed the mixture with a nitrogen stream for 30 min
  2. additionThen, Pd(dppf)Cl2 was added
  3. customthe flask sealed
  4. temperatureThe mixture was cooled
  5. filtrationfiltered through Florisil
  6. customEvaporation under vacuum

Sources & evidence

ORD record
ord-3556cb34de5947d282ebe3119cce1597
Source dataset
uspto-grants-2015_02
Patent number
US08946425B2

Reaction notes

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