3-Amino-2-bromopyridine → HCID 89930616, compound

HRID 714135Notes

Reaction equation

HRID 714135 reaction equation
[C:1]([O:5][C:6](=[O:30])[NH:7][C@@H:8]([C:28]#[CH:29])[CH2:9][O:10][Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:32]1[C:37]([NH2:38])=[CH:36][CH:35]=[CH:34][N:33]=1>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.C(#N)C>[C:1]([O:5][C:6](=[O:30])[NH:7][C@@H:8]([C:28]#[C:29][C:32]1[C:37]([NH2:38])=[CH:36][CH:35]=[CH:34][N:33]=1)[CH2:9][O:10][Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 6428163-Amino-2-bromopyridineHCID 89930615HCID 89930615, compound

Product 1

HCID 89930616HCID 89930616, compoundYield 99.5%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of tert-butyl[(2S)-1-{[tert-butyl(diphenyl)silyl]oxy}but-3-yn-2-yl]carbamate (30, 144 mg, 0.340 mmol), 2-bromopyridin-3-amine (53 mg, 0.306 mmol) (or any other suitable halide or triflate ester) and bis(triphenylphosphine)palladium(II) dichloride (18 mg, 0.026 mmol) was dissolved in degassed dry TEA (1.2 mL, 8.61 mmol) and acetonitrile (0.6 ml), stirred for 5 minutes at room temperature and treated with copper(I) iodide (7 mg, 0.037 mmol). The final mixture was placed in a preheated oil bath at +52° C. and further stirred under N2 in the dark for 4.5 h, concentrated and submitted to purification through a chromatographic cartridge of silicagel (12 g) eluted with 0.5% to 12% MeOH in DCM (UV detection at 254 nm) to give title compound (157 mg, 99% yield) as a brown solid. MS: m/z=516.3 (MH+).

Workup

  1. dissolutionwas dissolved
  2. stirringfurther stirred under N2 in the dark for 4.5 h
  3. concentrationconcentrated
  4. customsubmitted to purification through a chromatographic cartridge of silicagel (12 g)
  5. washeluted with 0.5% to 12% MeOH in DCM (UV detection at 254 nm)

Sources & evidence

ORD record
ord-23f31a8581a04fcd8d262889de2c2616
Source dataset
uspto-grants-2015_11
Patent number
US09187415B2

Reaction notes

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