Triethyl borate → HCID 57936314, compound

HRID 1435024Notes

Reaction equation

HRID 1435024 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.BrN1C(=O)CCC1=O.C(OB(OCC)OCC)C.B(O)O.Cl[C:33]1[CH:38]=[CH:37][N:36]=[C:35]([NH:39][CH:40]2[CH2:45][C:44]([CH3:47])([CH3:46])[NH:43][C:42]([CH3:49])([CH3:48])[CH2:41]2)[N:34]=1>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:37]2[CH:38]=[CH:33][N:34]=[C:35]([NH:39][CH:40]3[CH2:45][C:44]([CH3:47])([CH3:46])[NH:43][C:42]([CH3:49])([CH3:48])[CH2:41]3)[N:36]=2)=[CH:3]1

Participants

8

Reactant 5

HCID 9009Triethyl borateHCID 117811-MethylindoleHCID 61668Boronic AcidHCID 67184N-bromobutanimideHCID 57936167(4-Chloro-pyrimidin-2-yl)(2,2,6,6-tetramethyl-piperidin-4-yl)-amine

Product 1

HCID 57936314HCID 57936314, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-Methyl-indole (1.00 g, 3.81 mmol) in 30 ml of THF was added 1-bromo-pyrrolidine-2,5-dione (1.36 g, 3.81 mmol) and the mixture was stirred for 2 hours. The reaction mixture was poured into 200 ml of hexanes and purified by filtration over a short plug of silicagel (Ether/hexanes:1/1). The solution was concentrated close to dryness, redissolved in 25 ml of THF and cooled to −78° C. Tert.-butyllithium (5.08 ml of a 1.5M solution in pentane, 7.62 mmol) was added dropwise and stirred for 15 minutes. Then, triethylborate (0.65 ml, 3.81 mmol) was added in one portion and stirring was continued for 2 hours. The reaction was quenched with 3.5 ml of MeOH and 10 ml of water. The mixture was given into EtOAc and the aqueous layer was extracted with EtOAc. The combined organic phases were dried over sodium sulfate and evaporated to give a green suspension, which was used without further purification. The title compound was prepared analogous to Step C of Method C, starting from this crude boronic acid and (4-chloro-pyrimidin-2-yl)-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine using bis(triphenylphosphine)palladium(II) dichloride as a catalyst. Yield: 327 mg (48%).

Workup

  1. filtrationpurified by filtration over a short plug of silicagel (Ether/hexanes:1/1)
  2. concentrationThe solution was concentrated
  3. customclose to dryness
  4. dissolutionredissolved in 25 ml of THF
  5. additionTert.-butyllithium (5.08 ml of a 1.5M solution in pentane, 7.62 mmol) was added dropwise
  6. stirringstirred for 15 minutes
  7. stirringstirring
  8. waitwas continued for 2 hours
  9. customThe reaction was quenched with 3.5 ml of MeOH and 10 ml of water
  10. extractionthe aqueous layer was extracted with EtOAc
  11. dry with materialThe combined organic phases were dried over sodium sulfate
  12. customevaporated
  13. customto give a green suspension, which
  14. customwas used without further purification

Sources & evidence

ORD record
ord-24276be5cd744e43a731e595305f0112
Source dataset
uspto-grants-2009_11
Patent number
US07615562B2

Reaction notes

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