Cesium carbonate → (S)-2,2-difluoro-1-(2-((7-(4-(piperazin-1-yl)phenyl)pyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)ethanone

HRID 57634Notes

Reaction equation

HRID 57634 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][C@H:14]2[CH2:19][N:18]([C:20](=[O:24])[CH:21]([F:23])[F:22])[CH2:17][CH2:16][O:15]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][N:8]=2)[CH:3]=1.Cl.CC1(C)C(C)(C)OB([C:34]2[CH:39]=[CH:38][C:37]([N:40]3[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]3)=[CH:36][CH:35]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:22][CH:21]([F:23])[C:20]([N:18]1[CH2:17][CH2:16][O:15][C@@H:14]([CH2:13][NH:12][C:10]2[C:9]3[C:4](=[N:5][CH:6]=[CH:7][N:8]=3)[CH:3]=[C:2]([C:34]3[CH:35]=[CH:36][C:37]([N:40]4[CH2:41][CH2:42][NH:43][CH2:44][CH2:45]4)=[CH:38][CH:39]=3)[N:11]=2)[CH2:19]1)=[O:24]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 710936951-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine hydrochlorideHCID 86717397(S)-1-(2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)-2,2-difluoroethanone

Product 1

HCID 86717396(S)-2,2-difluoro-1-(2-((7-(4-(piperazin-1-yl)phenyl)pyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)ethanoneYield 108.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (S)-1-(2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)-2,2-difluoroethanone (70 mg, 0.19 mmol), 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine hydrochloride (96 mg, 0.29 mmol), Pd(PPh3)4 (45 mg, 0.04 mmol) and Cs2CO3 (191 mg, 0.59 mmol) in 8 mL of dioxane and 0.1 mL of water, under N2, was stirred at 110° C. overnight. The volatiles were removed in vacuo, and the residue was purified by chromatography with MeOH/H2O (1:10˜8:1) to give 100 mg of title compound.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was purified by chromatography with MeOH/H2O (1:10˜8:1)

Sources & evidence

ORD record
ord-e2c57a65713d4c87b6d407d7dc84ee55
Source dataset
uspto-grants-2016_09
Patent number
US09434726B2

Reaction notes

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