Dimethylformamide → HCID 86698497, compound

HRID 1773487Notes

Reaction equation

HRID 1773487 reaction equation
Br[C:2]1[N:30]=[CH:29][CH:28]=[CH:27][C:3]=1[C:4]([NH:6][C@H:7]([C:9]1[N:10]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:11](=[O:20])[C:12]2[C:17]([CH:18]=1)=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:19])[CH3:8])=[O:5].CN(C=O)C.[NH:36]1[CH:40]=[C:39](B(O)O)[CH:38]=[N:37]1.C([O-])([O-])=O.[Na+].[Na+]>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.CCO>[Cl:19][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:12]=1[C:11](=[O:20])[N:10]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:9]([C@@H:7]([NH:6][C:4](=[O:5])[C:3]1[CH:27]=[CH:28][CH:29]=[N:30][C:2]=1[C:39]1[CH:40]=[N:36][NH:37][CH:38]=1)[CH3:8])=[CH:18]2

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 177502781H-Pyrazole-4-boronic acidHCID 86698493HCID 86698493, compound

Product 1

HCID 86698497HCID 86698497, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (S)-2-bromo-N-(1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)nicotinamide (52) (125 mg, 0.26 mmol) in a 1:1 mixture of DMF and EtOH (9 mL), 1H-pyrazole-4-boronic acid (37 mg, 0.34 mmol), tetrakis(triphenylphosphine)palladium (0) (21 mg, 0.018 mmol) and aqueous Na2CO3 solution (1.0 M, 0.78 mL, 0.78 mmol) were added sequentially. The resulting mixture was stirred at 85° C. for 16 h. The mixture was allowed to cool to RT and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by prep-TLC plate (10% MeOH-DCM) to afford the product (S)-N-(1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)-2-(1H-pyrazol-4-yl)nicotinamide (compound 58). ESI-MS m/z: 471.0 [M+H]+.

Workup

  1. additionwere added sequentially
  2. temperatureto cool to RT
  3. custompartitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by prep-TLC plate (10% MeOH-DCM)

Sources & evidence

ORD record
ord-be6f824252e14cadbd391ae13ad760f9
Source dataset
uspto-grants-2016_02
Patent number
US09255108B2

Reaction notes

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