Sodium Carbonate → HCID 86698494, compound

HRID 1429706Notes

Reaction equation

HRID 1429706 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-33f290c6311c4661ae5330bf9fecd7cb
Source dataset
uspto-grants-2015_01
Patent number
US08940742B2

Reaction notes

Loading…