3-Bromo-5-methylpyridine → HCID 131734733, compound

HRID 1775331Notes

Reaction equation

HRID 1775331 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.CC(C)([O-])C.[Na+].[NH:15]1[CH2:19][CH2:18][C@H:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16]1.CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:8][C:6]1[CH:7]=[C:2]([N:15]2[CH2:19][CH2:18][C@H:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:24])[CH3:26])[CH2:16]2)[CH:3]=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 8177133-Bromo-5-methylpyridineHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 131734733HCID 131734733, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3-bromo-5-methylpyridine (138 mg, 0.892 mmol), sodium tert-butoxide (154 mg, 1.604 mmol), tert-butyl N-[(3S)-pyrrolidin-3-yl]carbamate (224 mg, 1.203 mmol) and 2-(dicyclohexylphosphino)-2′,6′-isopropoxybiphenyl (RuPhos, 37.4 mmol) in anhydrous 1,4-dioxane (7 ml) was purged with argon. Tris(dibenzylideneacetone)dipalladium (0) (Pd2(DBA)3, 73.5 mg, 0.08 mmol) was added and the mixture was stirred at 70° C. for two hours in a closed vial. After cooling to room temperature the mixture was filtered through kieselguhr and concentrated under reduced pressure. The residue was purified by column chromatography (silica, gradient from 0.5 to 7% methanol containing 7N NH3 in dichloromethane (DCM)) to afford 163 mg of a yellow solid (0.588 mmol, 73%) MS (ESI) 278.2 [M+1]+.

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. filtrationwas filtered through kieselguhr
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography (silica, gradient from 0.5 to 7% methanol containing 7N NH3 in dichloromethane (DCM))

Sources & evidence

ORD record
ord-8fbe72871a1c4190953b07e5852ef6a8
Source dataset
uspto-grants-2016_02
Patent number
US09260441B2

Reaction notes

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