Toluene → HCID 45137945, compound

HRID 2278753Notes

Reaction equation

HRID 2278753 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([N:19]2[CH2:23][CH2:22][CH2:21][C@H:20]2[CH2:24][OH:25])[CH:18]=1)[C:5]([NH:7][CH2:8][C:9]1[CH:10]=[N:11][C:12]([CH3:15])=[CH:13][CH:14]=1)=[O:6].B(O)(O)[C:27]1[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[OH:25][CH2:24][C@@H:20]1[CH2:21][CH2:22][CH2:23][N:19]1[C:17]1[CH:16]=[C:4]([C:5]([NH:7][CH2:8][C:9]2[CH:10]=[N:11][C:12]([CH3:15])=[CH:13][CH:14]=2)=[O:6])[CH:3]=[C:2]([C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)[CH:18]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 79799Tolylboronic acidHCID 58449375HCID 58449375, compound

Product 1

HCID 45137945HCID 45137945, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To a mixture of (S)-3-bromo-5-(2-(hydroxymethyl)pyrrolidin-1-yl)-N-((6-methylpyridin-3-yl)methyl)benzamide (65 mg, 0.16 mmol), p-tolylboronic acid (24 mg, 0.18 mmol), toluene (4 mL), cesium carbonate (57 mg, 0.18 mmol), and water (0.2 mL) under argon was added tetrakis(triphenylphosphine)palladium(0) (9.2 mg, 0.0080 mmol). The reaction mixture was heated under reflux for 5 h. After cooling, the mixture was filtered through Celite and the filter cake was washed with EtOAc. The filtrate was washed with brine, dried (Na2SO4), and concentrated. The residue was purified by preparative HPLC (100×21.2 mm C18 column, 30-80% CH3CN/water [10 mM Et2NH]) to afford a white foam.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 5 h
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered through Celite
  5. washthe filter cake was washed with EtOAc
  6. washThe filtrate was washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC (100×21.2 mm C18 column, 30-80% CH3CN/water [10 mM Et2NH])
  10. customto afford a white foam

Sources & evidence

ORD record
ord-e001c2ece5fc481bb3568d84f78b00d1
Source dataset
uspto-grants-2015_09
Patent number
US09133122B2

Reaction notes

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