Sodium Carbonate → HCID 68752963, compound

HRID 1051795Notes

Reaction equation

HRID 1051795 reaction equation
Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10]([N:12]1[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]1)=[N:9][C:8]([C@@H:19]([NH:21][C:22]1[N:30]=[CH:29][N:28]=[C:27]3[C:23]=1[N:24]=[CH:25][N:26]3[CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][O:32]1)[CH3:20])=[CH:7]2.[CH3:37][N:38]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[N:39]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]>[CH3:37][N:38]1[CH:42]=[C:41]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[C:10]([N:12]2[CH2:13][CH2:14][N:15]([CH3:18])[CH2:16][CH2:17]2)=[N:9][C:8]([C@@H:19]([NH:21][C:22]2[N:30]=[CH:29][N:28]=[C:27]4[C:23]=2[N:24]=[CH:25][N:26]4[CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][O:32]2)[CH3:20])=[CH:7]3)[CH:40]=[N:39]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 68753126HCID 68753126, compound

Product 1

HCID 68752963HCID 68752963, compound

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

N—((S)-1-(8-chloro-1-(4-methylpiperazin-1-yl)isoquinolin-3-yl)ethyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine 140 (80 mg, 0.16 mmol, 1.0 eq), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (66 mg, 0.32 mmol, 2.0 eq), PdCl2(dppf) (13 mg, 0.016 mmol, 0.1 eq) and Na2CO3 (84 mg, 0.79 mmol, 5.0 eq) were 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 then 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, N—((S)-1-(8-(1-methyl-1H-pyrazol-4-yl)-1-(4-methylpiperazin-1-yl)isoquinolin-3-yl)ethyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine 141.

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-0a9f8c5e10ed4b4fb5debd2a2392b349
Source dataset
uspto-grants-2016_07
Patent number
US09388183B2

Reaction notes

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