1-Hexyne → 1-tert-butyl 3-methyl (3R,5S)-5-{[(2-tert-butyl-4-(hex-1-yn-1-yl)pyrimidin-5-yl)carbonyl](2-methylpropyl)amino}piperidine-1,3-dicarboxylate

HRID 1260034Notes

Reaction equation

HRID 1260034 reaction equation
[C:1]([C:5]1[N:10]=[C:9](Cl)[C:8]([C:12]([N:14]([CH2:32][CH:33]([CH3:35])[CH3:34])[C@@H:15]2[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18][C@H:17]([C:28]([O:30][CH3:31])=[O:29])[CH2:16]2)=[O:13])=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[CH:45]#[C:46][CH2:47][CH2:48][CH2:49][CH3:50]>CN(C=O)C.[Cu](I)I>[C:1]([C:5]1[N:10]=[C:9]([C:45]#[C:46][CH2:47][CH2:48][CH2:49][CH3:50])[C:8]([C:12]([N:14]([CH2:32][CH:33]([CH3:35])[CH3:34])[C@@H:15]2[CH2:20][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:18][C@H:17]([C:28]([O:30][CH3:31])=[O:29])[CH2:16]2)=[O:13])=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 127321-HexyneHCID 81531DiisopropylethylamineHCID 593565701-tert-butyl 3-methyl (3R*,5S*)-5-{[(2-tert-butyl-4-chloropyrimidin-5-yl)carbonyl](isobutyl)amino}piperidine-1,3-dicarboxylate

Product 1

HCID 583551461-tert-butyl 3-methyl (3R,5S)-5-{[(2-tert-butyl-4-(hex-1-yn-1-yl)pyrimidin-5-yl)carbonyl](2-methylpropyl)amino}piperidine-1,3-dicarboxylate

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Procedure

1-tert-Butyl 3-methyl(3R,5S)-5-{[(2-tert-butyl-4-chloropyrimidin-5-yl)carbonyl](isobutyl)amino}piperidine-1,3-dicarboxylate (300 mg), dichloro[bis(triphenylphosphine)]palladium (412 mg), copper iodide (112 mg) and N,N-diisopropylethylamine (0.51 μL) were dissolved in DMF (8 ml), and the mixture was stirred at room temperature for 15 min. 1-Hexyne (0.08 ml) was added and the mixture was stirred at room temperature 2 hr, and further at 70° C. for 8 hr. The mixture was cooled to room temperature, adsorbed to silica gel (10 g), and a fraction eluted with ethyl acetate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with hexane-ethyl acetate (95:5-30:70) was concentrated under reduced pressure to give the object product (218 mg).

Workup

  1. stirringthe mixture was stirred at room temperature 2 hr
  2. waitfurther at 70° C. for 8 hr
  3. temperatureThe mixture was cooled to room temperature
  4. washa fraction eluted with ethyl acetate
  5. concentrationwas concentrated under reduced pressure
  6. washa fraction eluted with hexane-ethyl acetate (95:5-30:70)
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-b6fcf9a1a70f4e7bacfd8003e02757f3
Source dataset
uspto-grants-2013_06
Patent number
US08466282B2

Reaction notes

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