Triethylamine → tert-butyl (2R,5S)-2-[(2-aminopyridin-3-yl)ethynyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate

HRID 629705Notes

Reaction equation

HRID 629705 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[N:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][C@@H:13]([C:23]#[CH:24])[O:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[C:26]1[C:27]([NH2:32])=[N:28][CH:29]=[CH:30][CH:31]=1.C(N(CC)CC)C>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[NH2:32][C:27]1[C:26]([C:24]#[C:23][C@H:13]2[O:12][CH2:11][C@@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[N:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14]2)=[CH:31][CH:30]=[CH:29][N:28]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 8177002-Amino-3-bromopyridineHCID 86726312Tert-butyl (2R,5S)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-ethynylmorpholine-4-carboxylate

Product 1

HCID 86726311tert-butyl (2R,5S)-2-[(2-aminopyridin-3-yl)ethynyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A solution of tert-butyl (2R,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-ethynylmorpholine-4-carboxylate (1 eq) and 3-bromopyridin-2-amine (1.4 eq) in acetonitrile (0.1M) and triethylamine (25 eq) was flushed with nitrogen for 10 minutes. Then bis(triphenylphosphine)palladium(ii) chloride (0.1 eq) and copper(i) iodide (1.2 eq) were added and the mixture was flushed again with nitrogen for 10 minutes. The reaction mixture was stirred at 60° C. for 2 hours in the dark. It was concentrated to dryness and the residue was purified by automated SiO2 flash chromatography system using solvent gradient of 0% to 10% MeOH/CH2Cl2 to afford the desired compound.

Workup

  1. customthe mixture was flushed again with nitrogen for 10 minutes
  2. concentrationIt was concentrated to dryness
  3. customthe residue was purified by automated SiO2 flash chromatography system

Sources & evidence

ORD record
ord-46c83fafaec84219823ccf49b3d9f004
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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