Sodium Carbonate → 2-methyl-2-[5-(1H-pyrazolo[3,4-b]pyridin-4-yl)-3-thienyl]butanenitrile

HRID 44684Notes

Reaction equation

HRID 44684 reaction equation
Br[C:2]1[S:6][CH:5]=[C:4]([C:7]([CH3:12])([CH2:10][CH3:11])[C:8]#[N:9])[CH:3]=1.CC1(C)C(C)(C)OB([C:21]2[CH:26]=[CH:25][N:24]=[C:23]3[N:27](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:28]=[CH:29][C:22]=23)O1.C([O-])([O-])=O.[Na+].[Na+].O.CCOC(C)=O>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH:27]1[C:23]2=[N:24][CH:25]=[CH:26][C:21]([C:2]3[S:6][CH:5]=[C:4]([C:7]([CH3:12])([CH2:10][CH3:11])[C:8]#[N:9])[CH:3]=3)=[C:22]2[CH:29]=[N:28]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 22728543Water ethylacetateHCID 57969821HCID 57969821, compoundHCID 666434652-(5-Bromothiophen-3-yl)-2-methylbutanenitrile

Product 1

HCID 666460942-methyl-2-[5-(1H-pyrazolo[3,4-b]pyridin-4-yl)-3-thienyl]butanenitrileYield 26%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-(5-bromo-3-thienyl)-2-methyl-butanenitrile (789 mg, 3.232 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-trityl-pyrazolo[3,4-b]pyridine (1.750 g, 3232 mmol), Na2CO3 (4.848 mL of 2 M, 9.696 mmol) and tetrakis(triphenylphosphine) palladium(0) (112.0 mg, 0.09696 mmol) in DME (12 mL) was heated at 150° C. for 10 minutes in the microwave. The mixture was treated with water/EtOAc and the two layers separated. The organics were dried (MgSO4), filtered, concentrated and the resultant residue was dissolved in DCM (8 mL) and treated with triethylsilane (5 mL) and TFA (1.5 mL) at RT. The reaction was allowed to stir for 2 hours, concentrated in vacuo and purified by column chromatography (1:1 to 2:1 Petroleum ether/EtOAc) to give the required product (236 mg, 26% Yield). 1H NMR (CDCl3, 400 MHz) δ 1.06 (3H, m), 1.78 (3H, s), 2.05 (2H, m), 7.49 (1H, m), 7.53 (1H, m), 7.63 (1H, m), 8.42 (1H, m), 8.60 (1H, m); MS (ES+) 283.09

Workup

  1. customthe two layers separated
  2. dry with materialThe organics were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionthe resultant residue was dissolved in DCM (8 mL)
  6. additiontreated with triethylsilane (5 mL) and TFA (1.5 mL) at RT
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography (1:1 to 2:1 Petroleum ether/EtOAc)

Sources & evidence

ORD record
ord-0479c8226da04acc9408bea70e1db447
Source dataset
uspto-grants-2013_09
Patent number
US08541445B2

Reaction notes

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