Sodium Carbonate → HCID 66615542, compound

HRID 869469Notes

Reaction equation

HRID 869469 reaction equation
[NH2:1][C@H:2]([C:4]1[N:5]([CH:16]2[CH2:18][CH2:17]2)[C:6](=[O:15])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2Cl)[CH3:3].[CH3:19][N:20]1[CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:22]=[N:21]1.C([O-])([O-])=O.[Na+].[Na+]>CC(N(C)C)=O.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@H:2]([C:4]1[N:5]([CH:16]2[CH2:18][CH2:17]2)[C:6](=[O:15])[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2[C:23]1[CH:22]=[N:21][N:20]([CH3:19])[CH:24]=1)[CH3:3]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 66615508HCID 66615508, compound

Product 1

HCID 66615542HCID 66615542, 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 mixture of (S)-3-(1-aminoethyl)-8-chloro-2-cyclopropylisoquinolin-1(2H)-one II-6 (878 mg, 3.35 mmol, 1.0 eq) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (815 mg, 3.92 mmol, 1.2 eq) in anhydrous DMA (10 mL) in a sealed tube, PdCl2(dppf) (219 mg, 0.27 mmol, 0.08 eq) and aqueous Na2CO3 solution (1 M, 10.0 mL, 10.0 mmol, 3.0 eq) were added and the resulting mixture was stirred at 120° C. for 3 h. The reaction mixture was allowed to cool to RT, quenched with water, and then extracted with ethyl acetate (200 mL×3). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO (silica gel cartridge, 0-8% MeOH-DCM) to afford the product, (S)-3-(1-aminoethyl)-2-cyclopropyl-8-(1-methyl-1H-pyrazol-4-yl)isoquinolin-1(2H)-one II-12 as a pink/magenta solid. ESI-MS m/z: 309.2 [M+H]+.

Workup

  1. temperatureto cool to RT
  2. customquenched with water
  3. extractionextracted with ethyl acetate (200 mL×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by ISCO (silica gel cartridge, 0-8% MeOH-DCM)

Sources & evidence

ORD record
ord-ca6e061fd26d4fc2b01a8a7a8515b704
Source dataset
uspto-grants-2015_03
Patent number
US08969363B2

Reaction notes

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