Diisopropylethylamine → 2-(4-chloro-1-methyl-1H-pyrazol-5-yl)-6-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

HRID 339994Notes

Reaction equation

HRID 339994 reaction equation
Br[C:2]1[N:7]=[C:6]2[CH2:8][N:9]([C@@H:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH2:13][OH:14])[C:10](=[O:11])[C:5]2=[CH:4][CH:3]=1.[Cl:23][C:24]1[CH:25]=[N:26][N:27]([CH3:38])[C:28]=1B1OC(C)(C)C(C)(C)O1.C(N(CC)C(C)C)(C)C>O1CCOCC1.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:23][C:24]1[CH:25]=[N:26][N:27]([CH3:38])[C:28]=1[C:2]1[N:7]=[C:6]2[CH2:8][N:9]([C@@H:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH2:13][OH:14])[C:10](=[O:11])[C:5]2=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 755256674-chloro-1-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866814792-bromo-6-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one

Product 1

HCID 866814812-(4-chloro-1-methyl-1H-pyrazol-5-yl)-6-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-oneYield 70.3%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

In one 20 mL vial, a mixture of 2-bromo-6-[(1S)-1-(3-fluorobenzyl)-2-hydroxyethyl]-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (0.041 g, 0.11 mmol), 4-chloro-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.0327 g, 0.135 mmol), bis(tri-t-butylphosphine)palladium (0.00574 g, 0.0112 mmol), and N,N-diisopropylethylamine (0.0587 mL, 0.337 mmol) in 1,4-dioxane (5 mL) was microwaved at 120° C. for 20 minutes. The resulting mixture was filtered through a pad of celite and concentrated, and the residue was purified by combi-flash chromatography using hexane/EtOAc/methanol to give 31 mg (68% yield) of the final product. LC/MS found: 401.1 (M+H)+.

Workup

  1. customwas microwaved at 120° C. for 20 minutes
  2. filtrationThe resulting mixture was filtered through a pad of celite
  3. concentrationconcentrated
  4. customthe residue was purified by combi-flash chromatography

Sources & evidence

ORD record
ord-0cc48ce58db048c5ae33e6373bff05dd
Source dataset
uspto-grants-2014_11
Patent number
US08895571B2

Reaction notes

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