3-Bromo-5-methylpyridine → tert-Butyl N-methyl-N-[2-[methyl-(5-methyl-3-pyridyl)amino]ethyl]carbamate

HRID 631823Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[CH3:9][N:10]([CH2:18][CH2:19][NH:20][CH3:21])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14].CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:9][N:10]([CH2:18][CH2:19][N:20]([CH3:21])[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 100 °C

Procedure

3-Bromo-5-methylpyridine (350 mg, 2.035 mmol), tert-butyl N-methyl-N-(2-methylaminoethyl)carbamate (686 mg, 3.05 mmol), RuPhos (47.5 mg, 0.102 mmol) and sodium tert-butoxide (489 mg, 5.09 mmol) were combined in anhydrous toluene (15 ml). The mixture was purged with argon, tris(dibenzylideneacetone)dipalladium (0) chloroform complex (105 mg, 0.102 mmol) was added and the mixture was stirred at 100° C. overnight. The mixture was filtered through kieselguhr, concentrated under reduced pressure and the residue was purified by column chromatography (silica, gradient of 10 to 50% ethyl acetate in heptane) to yield 301 mg (1.078 mmol, 53%) MS(ESI) m/z=280.2 [M+1]+.

Workup

additionwas added
filtrationThe mixture was filtered through kieselguhr
concentrationconcentrated under reduced pressure
customthe residue was purified by column chromatography (silica, gradient of 10 to 50% ethyl acetate in heptane)
customto yield 301 mg (1.078 mmol, 53%) MS(ESI) m/z=280.2 [M+1]+

Sources & evidence

ORD record: ord-77721046e93a43d5a6d4bd21ad4f321d
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321724B2

Reaction notes

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