tert-butyl N-(prop-2-yn-1-yl)carbamate → tert-Butyl 3-(2-amino-4-chloro-6-methylpyrimidin-5-yl)prop-2-ynylcarbamate

HRID 1617139Notes

Reaction equation

[CH2:1]([NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8])[C:2]#[CH:3].[Cl:12][C:13]1[C:18](I)=[C:17]([CH3:20])[N:16]=[C:15]([NH2:21])[N:14]=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>[NH2:21][C:15]1[N:14]=[C:13]([Cl:12])[C:18]([C:3]#[C:2][CH2:1][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:8])([CH3:10])[CH3:9])=[C:17]([CH3:20])[N:16]=1

Participants

Conditions

Temperature: 70 °C

Procedure

tert-Butyl prop-2-ynylcarbamate (3.11 g), 4-chloro-5-iodo-6-methylpyrimidin-2-amine (1.8 g) and bis(triphenylphosphine)palladium(II) chloride (0.469 g) were combined in TEA (100 mL). The reaction mixture was purged with nitrogen gas for 3 min then copper(I) iodide (0.254 g) added. The resulting mixture was stirred at 70° C. for 16 h, then cooled to rt and filtered. The filtrate was washed with water and brine, dried and the solvents evaporated. The crude material was dissolved in MeOH (20 mL), acidified with acetic acid (1 mL) and purified by SCX and further purified by chromatography eluting 10% MeOH and 0.25% Ammonia (7N) in DCM to afford the subtitle compound 0.93 g.

Workup

customThe reaction mixture was purged with nitrogen gas for 3 min
additioncopper(I) iodide (0.254 g) added
temperaturecooled to rt
filtrationfiltered
washThe filtrate was washed with water and brine
customdried
customthe solvents evaporated
dissolutionThe crude material was dissolved in MeOH (20 mL)
custompurified by SCX
customfurther purified by chromatography
washeluting 10% MeOH and 0.25% Ammonia (7N) in DCM

Sources & evidence

ORD record: ord-897741a5475f4b26aec29e2304e6a768
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765939B2

Reaction notes

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