1-Methyl-1H-indole-5-boronic acid → ethyl 2-methyl-4-(1-methyl-1H-indol-5-yl)pyrimidine-5-carboxylate

HRID 1930387Notes

Reaction equation

HRID 1930387 reaction equation
C([O-])(O)=O.[Na+].C1(C)C=CC=CC=1.C(O)C.Cl[C:17]1[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:21][N:20]=[C:19]([CH3:28])[N:18]=1.[CH3:29][N:30]1[C:38]2[C:33](=[CH:34][C:35](B(O)O)=[CH:36][CH:37]=2)[CH:32]=[CH:31]1>C(OCC)(=O)C.O.[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>[CH3:28][C:19]1[N:18]=[C:17]([C:35]2[CH:34]=[C:33]3[C:38](=[CH:37][CH:36]=2)[N:30]([CH3:29])[CH:31]=[CH:32]3)[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:21][N:20]=1

Participants

7

Reactant 3

HCID 27598671-Methyl-1H-indole-5-boronic acidHCID 12677176Ethyl 4-chloro-2-methylpyrimidine-5-carboxylateHCID 86620166NaHCO3 toluene ethanol

Product 1

HCID 69037048ethyl 2-methyl-4-(1-methyl-1H-indol-5-yl)pyrimidine-5-carboxylateYield 53%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

In a mixture of saturated NaHCO3:toluene:ethanol (1:2:1) (12 mL) was dissolved ethyl 4-chloro-2-methylpyrimidine-5-carboxylate (500 mg, 2.49 mmol), N-methylindole-5-boronic acid (872 mg, 4.98 mmol) and to this was added tetrakis(triphenylphosphine)-palladium(0) (58 mg). The reaction stirred at 75° C., under Ar, overnight. The reaction was allowed to cooled to RT, diluted with ethyl acetate (25 mL) and water (25 mL) and filtered free of insolubles. The organic phase was washed with 5% citric acid (25 mL), saturated sodium bicarbonate (25 mL) and brine (25 mL), evaporated at reduced pressure to give a reddish thick foam, and purified by chromatography (Biotage Si-25 column, 15-40% ethyl acetate/hexane) to give ethyl 2-methyl-4-(1-methyl-1 H-indol-5-yl)pyrimidine-5-carboxylate as a thick clear oil. The oil solidified overnight (391 mg, 53% yield). MS (ESI) m/z: 296.0 (M+H+).

Workup

  1. temperatureto cooled to RT
  2. filtrationfiltered free of insolubles
  3. washThe organic phase was washed with 5% citric acid (25 mL), saturated sodium bicarbonate (25 mL) and brine (25 mL)
  4. customevaporated at reduced pressure
  5. customto give a reddish thick foam
  6. custompurified by chromatography (Biotage Si-25 column, 15-40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-109fc1e01d8542ecb36f81c627129614
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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