Water → 5-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]isoindolin-1-one

HRID 339967Notes

Reaction equation

HRID 339967 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:16])[C:6]=1B1OC(C)(C)C(C)(C)O1.Br[C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[C:23](=[O:27])[N:22]([C@@H:28]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=1)[CH2:29][OH:30])[CH2:21]2.C(N(CC)C(C)C)(C)C.O1CCOCC1.O>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:16])[C:6]=1[C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[C:23](=[O:27])[N:22]([C@@H:28]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=1)[CH2:29][OH:30])[CH2:21]2

Participants

7

Reactant 5

HCID 962WaterHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 755256674-chloro-1-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866814615-bromo-2-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]isoindolin-1-one

Product 1

HCID 866814605-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]isoindolin-1-oneYield 67%

Reagents, catalysts & solvents 1

HCID 178418851HCID 178418851, compoundCatalyst

Procedure

A mixture of 4-chloro-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (177.0 mg, 0.7297 mmol), bis(tri-t-butylphosphine)palladium (31.1 mg, 0.0608 mmol), 5-bromo-2-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]isoindolin-1-one (220.0 mg, 0.6081 mmol) and N,N-diisopropylethylamine (0.318 mL, 1.82 mmol) in 1,4-dioxane (3 mL, 40 mmol) and water (150 μL, 8.3 mmol) was microwaved at 110° C. for 15 minutes. The reaction mixture was filtered through a pad of celite and the filtrate was concentrated under reduced pressure. The residue was purified by combi-flash chromatography eluting with EtOAc/hexane (30-100%) to give 0.162 g (67% yield) of the desired product as yellowish solid. LC/MS found: 399.9 (M+1)+.

Workup

  1. customwas microwaved at 110° C. for 15 minutes
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by combi-flash chromatography
  5. washeluting with EtOAc/hexane (30-100%)

Sources & evidence

ORD record
ord-86e767b71405491c9041125255a171a1
Source dataset
uspto-grants-2014_11
Patent number
US08895571B2

Reaction notes

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