Sodium Carbonate → HCID 71232740, compound

HRID 869468Notes

Reaction equation

HRID 869468 reaction equation
Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:8]([C@@H:19]([NH:21][C:22]1[N:27]3[N:28]=[CH:29][CH:30]=[C:26]3[N:25]=[CH:24][CH:23]=1)[CH3:20])=[CH:7]2.[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C)C(=O)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]>[CH3:31][N:32]1[CH:36]=[C:35]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[C:10](=[O:12])[N:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8]([C@@H:19]([NH:21][C:22]2[N:27]4[N:28]=[CH:29][CH:30]=[C:26]4[N:25]=[CH:24][CH:23]=2)[CH3:20])=[CH:7]3)[CH:34]=[N:33]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 71232739HCID 71232739, compound

Product 1

HCID 71232740HCID 71232740, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-8-chloro-2-phenyl-3-(1-(pyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)isoquinolin-1(2H)-one II-2 (66 mg, 0.158 mmol, 1.0 eq), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (66 mg, 0.316 mmol, 2.0 eq), PdCl2(dppf) (13 mg, 0.016 mmol, 0.1 eq) and Na2CO3 (84 mg, 0.79 mmol, 5.0 eq) was suspended in a mixture of N,N-dimethylacetamide (5 mL) and water (2 mL). The resulting mixture was degassed and back-filled with argon three times and stirred at 80° C. under argon overnight. The mixture was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (1-5% MeOH-DCM) to afford the product, (S)-8-(1-methyl-1H-pyrazol-4-yl)-2-phenyl-3-(1-(pyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)isoquinolin-1(2H)-one II-5 (43 mg, 60% yield). ESI-MS m/z: 462.2 [M+H]+.

Workup

  1. customThe resulting mixture was degassed
  2. additionback-filled with argon three times
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue was purified by flash column chromatography on silica gel (1-5% MeOH-DCM)

Sources & evidence

ORD record
ord-089e1328a99a40249be972543da33d0a
Source dataset
uspto-grants-2015_03
Patent number
US08969363B2

Reaction notes

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