Sodium Carbonate → HCID 86698494, compound

HRID 1773485Notes

Reaction equation

HRID 1773485 reaction equation
[NH2:1][C:2]1[C:3]([C:8]([NH:10][C@H:11]([C:13]2[N:14]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:15](=[O:24])[C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][C:17]=3Cl)[CH3:12])=[O:9])=[N:4][CH:5]=[CH:6][N:7]=1.[CH3:31][N:32]1[CH:36]=[C:35](B(O)O)[CH:34]=[N:33]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C)C(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[C:3]([C:8]([NH:10][C@H:11]([C:13]2[N:14]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:15](=[O:24])[C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[CH:18][C:17]=3[C:35]2[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=2)[CH3:12])=[O:9])=[N:4][CH:5]=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 112635011-Methyl-1H-pyrazole-4-boronic acidHCID 72188486HCID 72188486, compound

Product 1

HCID 86698494HCID 86698494, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (S)-3-amino-N-(1-(8-chloro-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)pyrazine-2-carboxamide (4) (100 mg, 0.24 mmol) in anhydrous N,N-dimethylacetamide (6 mL), 1-methyl-1H-pyrazol-4-ylboronic acid (78 mg, 0.4762 mmol), PdCl2(dppf) (16 mg, 0.019 mmol) and aqueous Na2CO3 solution (1.0 M, 0.72 mL, 0.72 mmol) were added sequentially. The resulting mixture was purged with argon and then stirred at 120° C. under argon for 17 h. The mixture was allowed to cool to RT and ice-water was added. The precipitate was collected by filtration, rinsed with water and dried in vacuo. The solid collected was further purified by ISCO column chromatography (silica gel cartridge, 0-8% MeOH/DCM) to afford the product (S)-3-amino-N-(1-(8-(1-methyl-1H-pyrazol-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)pyrazine-2-carboxamide (compound 54). ESI-MS m/z: 466.2 [M+H]+.

Workup

  1. customThe resulting mixture was purged with argon
  2. temperatureto cool to RT
  3. additionice-water was added
  4. filtrationThe precipitate was collected by filtration
  5. washrinsed with water
  6. customdried in vacuo
  7. customThe solid collected
  8. customwas further purified by ISCO column chromatography (silica gel cartridge, 0-8% MeOH/DCM)

Sources & evidence

ORD record
ord-d4a22ea9999f460b81b9e9b871794df6
Source dataset
uspto-grants-2016_02
Patent number
US09255108B2

Reaction notes

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