Toluene → HCID 45137949, compound

HRID 2278755Notes

Reaction equation

HRID 2278755 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].[CH3:26][C:27]1[CH:28]=[CH:29][C:30]([Sn](CCCC)(CCCC)CCCC)=[N:31][CH:32]=1.C1(C)C=CC=CC=1>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>[OH:25][CH2:24][C@H:20]1[CH2:21][CH2:22][CH2:23][N:19]1[C:17]1[CH:16]=[C:4]([CH:3]=[C:2]([C:30]2[CH:29]=[CH:28][C:27]([CH3:26])=[CH:32][N:31]=2)[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]

Participants

5

Reactant 3

HCID 1140TolueneHCID 111327115-Methyl-2-(tri-n-butylstannyl)pyridineHCID 67387487HCID 67387487, compound

Product 1

HCID 45137949HCID 45137949, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A mixture of (R)-3-bromo-5-(2-(hydroxymethyl)pyrrolidin-1-yl)-N-((6-methylpyridin-3-yl)methyl)benzamide (55 mg, 0.14 mmol), 5-methyl-2-(tributylstannyl)pyridine (65 mg, 0.16 mmol), Tetrakis(triphenylphosphine)palladium(0) (7.8 mg, 0.0068 mmol) and Toluene (1.5 mL, 14 mmol) under argon was subjected to microwave irradiation at 160° C. for 1 hour. The mixture was cooled to room temperature. Solvent was removed in vacuo and the residue was rinsed with hexane and then dissolved in MeOH and filtered. The filtrate was purified by preparative HPLC (100×21.2 mm C18 column, 20-70% CH3CN/water [10 mM Et2NH]) to afford a white foam. LC-MS: 1.64 min, 417.3 [M+1]+; HPLC: 6.76 min.

Workup

  1. customirradiation at 160° C. for 1 hour
  2. customSolvent was removed in vacuo
  3. washthe residue was rinsed with hexane
  4. dissolutiondissolved in MeOH
  5. filtrationfiltered
  6. customThe filtrate was purified by preparative HPLC (100×21.2 mm C18 column, 20-70% CH3CN/water [10 mM Et2NH])
  7. customto afford a white foam
  8. custom1.64 min, 417.3 [M+1]+
  9. custom6.76 min.

Sources & evidence

ORD record
ord-085d3ff31e824a618f7434de9f97188c
Source dataset
uspto-grants-2015_09
Patent number
US09133122B2

Reaction notes

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