Cesium carbonate → Tert-butyl 3-((7-(4-((2-ethoxy-2-oxoethyl)(methyl)amino)phenyl)pyrido[4,3-b]pyrazin-5-ylamino)methyl)-4,4-difluoropiperidine-1-carboxylate

HRID 57650Notes

Reaction equation

HRID 57650 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][CH2:13][CH:14]2[C:19]([F:21])([F:20])[CH2:18][CH2:17][N:16]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:15]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][N:8]=2)[CH:3]=1.[CH3:29][N:30]([C:37]1[CH:42]=[CH:41][C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][CH:38]=1)[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33].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>[CH2:35]([O:34][C:32](=[O:33])[CH2:31][N:30]([CH3:29])[C:37]1[CH:42]=[CH:41][C:40]([C:2]2[N:11]=[C:10]([NH:12][CH2:13][CH:14]3[C:19]([F:20])([F:21])[CH2:18][CH2:17][N:16]([C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH2:15]3)[C:9]3[C:4](=[N:5][CH:6]=[CH:7][N:8]=3)[CH:3]=2)=[CH:39][CH:38]=1)[CH3:36]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 71114141HCID 71114141, compoundHCID 86706994HCID 86706994, compound

Product 1

HCID 71114142Tert-butyl 3-((7-(4-((2-ethoxy-2-oxoethyl)(methyl)amino)phenyl)pyrido[4,3-b]pyrazin-5-ylamino)methyl)-4,4-difluoropiperidine-1-carboxylateYield 155.6%

Reagents, catalysts & solvents 3

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

Procedure

A solution of tert-butyl 3-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)-4,4-difluoropiperidine-1-carboxylate (173 mg, 0.42 mmol), ethyl 2-(methyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)amino)acetate (200 mg, 0.63 mmol), Pd(PPh3)4 and Cs2CO3 in 4 mL of dioxane and 0.5 mL of water was stirred at 160° C. for 1 hour. The volatiles were removed in vacuo, and the residue was purified by chromatography with MeOH/H2O (1:8˜5:1) to give 373 mg of title compound.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was purified by chromatography with MeOH/H2O (1:8˜5:1)

Sources & evidence

ORD record
ord-7c6bd0027a3a4f348eb1cadc6743c9dc
Source dataset
uspto-grants-2016_09
Patent number
US09434726B2

Reaction notes

Loading…