Water → HCID 45137948, compound

HRID 2278754Notes

Reaction equation

HRID 2278754 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+].O>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>[CH3:15][C:12]1[N:11]=[CH:10][C:9]([CH2:8][NH:7][C:5]([C:4]2[CH:3]=[C:2]([C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=3)[CH:18]=[C:17]([N:19]3[CH2:23][CH2:22][CH2:21][C@@H:20]3[CH2:24][OH:25])[CH:16]=2)=[O:6])=[CH:14][CH:13]=1

Participants

7

Reactant 5

HCID 962WaterHCID 1140TolueneHCID 10796Cesium carbonateHCID 79799Tolylboronic acidHCID 67387487HCID 67387487, compound

Product 1

HCID 45137948HCID 45137948, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

To a mixture of (R)-3-bromo-5-(2-(hydroxymethyl)pyrrolidin-1-yl)-N-((6-methylpyridin-3-yl)methyl)benzamide (45 mg, 0.11 mmol), p-tolylboronic acid (16 mg, 0.12 mmol), Toluene (3 mL, 30 mmol), cesium carbonate (4.0E1 mg, 0.12 mmol), and Water (0.2 mL, 8 mmol) under argon was added Tetrakis(triphenylphosphine)palladium(0) (6.4 mg, 0.0055 mmol). The 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. LC-MS: 2.09 min, 416.5 [M+1]+; HPLC: 9.12 min.

Workup

  1. temperatureThe 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
  11. custom2.09 min, 416.5 [M+1]+
  12. custom9.12 min.

Sources & evidence

ORD record
ord-bc4580c0ee2646a2b010311fc16e8c87
Source dataset
uspto-grants-2015_09
Patent number
US09133122B2

Reaction notes

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