Water → HCID 89600616, compound

HRID 2277681Notes

Reaction equation

HRID 2277681 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([Cl:18])[CH:14]=3)[C:9]2=[O:19])[CH:5]=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[NH:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.O>O1CCOCC1.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>[Cl:18][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:19])[N:8]([C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:29]3[CH:30]=[N:26][NH:27][CH:28]=3)[CH:3]=1)[CH2:17][CH2:16]2

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86685975HCID 86685975, compound

Product 1

HCID 89600616HCID 89600616, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

2-(5-Bromo-pyridin-3-yl)-6-chloro-3,4-dihydro-2H-isoquinolin-1-one (example 7) (34 mg, 0.1 mmol), Pd(PPh3)4 (5.8 mg, 0.005 mmol), K2CO3 (27.6 mg, 0.2 mmol) and 1H-pyrazole-4-boronic acid pinacol ester (29.1 mg, 0.15 mmol) were dissolved in dioxane (1 mL). The resulting reaction mixture was subject to microwave reaction at 150° C. for 45 min before it was poured into H2O (25 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was then purified by prep-HPLC to give title compound (9 mg, 28%) as a white solid. MS: 325.1 (M+H+).

Workup

  1. customThe resulting reaction mixture
  2. customreaction at 150° C. for 45 min before it
  3. extractionextracted with EtOAc (2×25 mL)
  4. washThe combined organic layers were washed with brine
  5. customdried over anhy
  6. filtrationNa2SO4, filtered
  7. concentrationconcentrated in vacuo
  8. customto give a crude product which
  9. customwas then purified by prep-HPLC

Sources & evidence

ORD record
ord-bc07dde2268a425c97d6d1e4a63e7d8e
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

Loading…